tag:blogger.com,1999:blog-34837514172180066822024-02-06T21:15:24.102-08:00Synthesis Of Drugssynthesis of drugs for medicinal use.Useful for pharmacy students.Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.comBlogger59125tag:blogger.com,1999:blog-3483751417218006682.post-62520073025084124512017-11-06T17:11:00.002-08:002017-11-06T17:17:43.600-08:00AICTE SPONSORED INTERNATIONAL SEMINAR ON HERBALS AND NATURAL PRODUCTS FOR LIVER AND PANCREATIC DISORDERS<div dir="ltr" style="text-align: left;" trbidi="on">
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Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-68278668455362135732014-07-13T04:58:00.000-07:002014-07-13T06:01:37.028-07:00Synthesis and Pharmacological Evaluation of Gastro-sparing Mutual Prodrug of Aceclofenac with Glucosamine<div dir="ltr" style="text-align: left;" trbidi="on">
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Suneela S. Dhaneshwar * 1, Sanal Dev1, B.Rathi2 and S. L. Bodhankar2<br />
1 Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy,<br />
Erandwane, Pune, India.<br />
2 Department of Pharmacology, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India.<br />
*Author for correspondence: Dr. Suneela Dhaneshwar E-mail: suneeladhaneshwar@rediffmail.com </div>
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InPharm Communique Vol 2, No 3 | 17</div>
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For full text of the article <a href="http://www.megafileupload.com/en/file/549708/Synthesis-of-Mutual-Prodrug-of-Aceclofenac-with-Glucosamine-pdf.html" target="_blank">CLICK HERE</a></div>
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<u>ABSTARCT </u></div>
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Aceclofenac is a nonsteroidal antiinflammatory drug that is used to relieve pain and inflammation in arthritic conditions like osteoarthritis, rheumatoid arthritis and ankylosing spodylitis. Aceclofenac is known to induce erosion and ulcers in the gastrointestinal tract but in contrast to other nonsteroidal anti-inflammatory agents, it has shown stimulatory effects on cartilage matrix synthesis. In order to lower the ulcerogenic potential and enhance effectiveness of aceclofenac as antiarthritic agent, a mutual prodrug was synthesized with neutraceutical carrier D-glucosamine that has shown to stimulate the biosynthesis of glucosaminoglycans and hyaluronic acid backbone needed for the formation of the proteoglycans found in the structural matrix of joints. The study showed that the prodrug not only lowered the ulcerogenic potential of aceclofenac but also enhanced its analgesic, antiinflammatory and antiarthritic activities thus proving the utility of D-glucosamine as an effective carrier in mutual prodrug synthesis. Key words Aceclofenac, anti-arthritic, anti-inflammatory, glucosamine, gastrosparing, mutual prodrug.</div>
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For full text of the article <a href="http://www.megafileupload.com/en/file/549708/Synthesis-of-Mutual-Prodrug-of-Aceclofenac-with-Glucosamine-pdf.html" target="_blank">CLICK HERE</a></div>
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Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-27737234459018399732012-10-17T07:29:00.000-07:002012-10-20T22:54:49.821-07:00Laboratory Synthesis Of Fenoverine<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="color: #444444;"> <u><b>Fenoverine Synthesis</b></u></span></div>
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" 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" /></a><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt;">MW: 459.57 MF:
C26H25N3O3S</span></span></div>
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<span style="color: #444444;"><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt;">LD50 <span style="mso-bidi-font-weight: bold;">Fenoverine</span>: 2874 mg/kg (M, p.o.)</span></span></div>
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<span style="color: #444444;"><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt;">IUPAC NAME <span style="mso-bidi-font-weight: bold;">Fenoverine:</span> <span style="mso-spacerun: yes;"> </span>10- [[4- (1 ,3- benzo dioxol- 5- yl methyl)-
1- piperazinyl ]acetyl]- 10 <i>H</i>- pheno thiazine</span></span></div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0in; mso-layout-grid-align: none; text-autospace: none;">
<span style="color: #444444;"><br /></span></div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0in; mso-layout-grid-align: none; text-autospace: none;">
<span style="color: #444444;"><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt;"><b><u>Reference </u></b></span></span></div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0in; mso-layout-grid-align: none; text-autospace: none;">
<span style="color: #444444;"><span style="font-family: "Times New Roman","serif"; font-size: 12.0pt;">French patent: 2092639 </span></span></div>
<span style="color: #444444;">
</span></div>
Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-73778471405672501852012-10-13T09:04:00.002-07:002012-10-13T09:04:45.889-07:00Laboratory Synthesis Of Fenbufen<div dir="ltr" style="text-align: left;" trbidi="on">
<h3 class="post-title entry-title" itemprop="name" style="text-align: center;">
<u><b>Fenbufen Synthesis</b></u></h3>
<div class="separator" style="clear: both; text-align: center;">
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<h3 class="post-title entry-title" itemprop="name" style="text-align: center;">
<span style="font-size: small;"><span style="font-weight: normal;">SYNTHESIS </span></span></h3>
<h3 class="post-title entry-title" itemprop="name" style="text-align: center;">
<span style="font-size: small;"><span style="font-weight: normal;">Tomeufeik, A.; et al. (American Cyanamid Co.); Compositions containing
substituted benzoylpropionic acids and method of use to treat
inflammation and pain. </span></span></h3>
<h3 class="post-title entry-title" itemprop="name" style="text-align: center;">
<span style="font-size: small;"><span style="font-weight: normal;"><u>REFERENCE </u></span></span></h3>
<ol style="text-align: left;">
<li><h3 class="post-title entry-title" itemprop="name">
<span style="font-size: small;"><span style="font-weight: normal;">Fenbufen. Drugs Fut 1976, 1, 1, 21<u> </u></span></span></h3>
</li>
<li><h3 class="post-title entry-title" itemprop="name">
<span style="font-size: small;"><span style="font-weight: normal;">DE 2147111; FR 2107848; GB 1320076; US 3784701 </span></span></h3>
<h3 class="post-title entry-title" itemprop="name">
<span style="font-size: small;"><span style="font-weight: normal;">MW: 254.29 MF: C16H14O3<br />LD50 Fenbufen : 795 mg/kg (M, p.o.);200 mg/kg (R, p.o.) </span></span></h3>
</li>
</ol>
</div>
Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-20774632113464185062012-08-15T10:45:00.000-07:002012-08-15T10:45:17.563-07:00VISUDHA YUDA SLEHA YUDE PRARTHANA<div dir="ltr" style="text-align: left;" trbidi="on">
This strong prayer is in malayalam. Say this prayer nine times a day for nine days . you will fulfill your prayer .<br />
Invite as many in here & spread the word.<br /> - Believer<br />
<div class="separator" style="clear: both; text-align: center;">
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<br />
</div>
Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-49330596412547823252012-08-15T10:40:00.002-07:002012-08-15T10:40:42.495-07:00<div dir="ltr" style="text-align: left;" trbidi="on">
<br /></div>
Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-78709565992731140942012-05-19T21:56:00.001-07:002012-11-01T20:11:50.422-07:00Laboratory Synthesis Of Ciprofloxacin<div dir="ltr" style="text-align: left;" trbidi="on">
<div>
<div style="text-align: center;">
<u><b> Ciprofloxacin Synthesis</b></u></div>
<div style="text-align: center;">
</div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0in; mso-layout-grid-align: none; text-autospace: none;">
<b><span style="font-family: "Arial","sans-serif"; font-size: 14pt;">Ciprofloxacin</span></b><span style="font-family: "Arial","sans-serif"; font-size: 10pt;"></span></div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0in; mso-layout-grid-align: none; text-autospace: none;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Use: antibacterial</span></div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: .0001pt; margin-bottom: 0in; mso-layout-grid-align: none; text-autospace: none;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;">LD50: 122 mg/kg (M, i.v.); 5 g/kg
(M, p.o.);</span><br />
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;"> </span><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">207 mg/kg (R, i.v.); >2 g/kg
(R, p.o.)</span></div>
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<br /></div>
<div class="MsoNormal" style="line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;"> </span><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">The condensation of
2,4-dichloro-5-fluorobenzoyl chloride (I) with diethyl malonate by means of
magnesium ethoxide in ether gives diethyl 2,4-dichloro-5-fluorobenzoylmalonate
(II), which is partially hydrolyzed and decarboxylated with p-toluenesulfonic
acid water yielding ethyl 2,4-dichloro-5-fluorobenzoylacetate . Condensation of
this with triethyl orthoformate in
refluxing acetic anhydride affords ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate
(III), which is treated with cyclopropylamine (IV) in ethanol to give ethyl
2-(2,4-dichloro-5-fluorobenzoyl)-3-cyclopropylaminoacrylate . The cyclization
of ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-cyclopropylaminoacrylate with NaH
in refluxing dioxane yields 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic
acid (V), which is finally condensed with piperazine in hot DMSO to afford the target compound
ciprofloxacin.</span></div>
<div style="text-align: center;">
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</div>
<div style="text-align: center;">
<br /></div>
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<br />
<u><b><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Synthesis references</span></b></u></div>
<ol style="text-align: left;">
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Reddy, P.G.;
Baskaran, S.; Microwave assisted amination of quinolone carboxylic acids: An
expeditious synthesis of fluoroquinolone antibacterials. <b>Tetrahedron Lett 2001,
42, 38, 6775</b></span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Drugs
Fut1984,9,(3):179</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">EP 0078362</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;"> JP 4253963</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">JP 58074667 </span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">US 4620007 </span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">US 4670444</span></li>
<li><span style="font-family: "Times New Roman","serif"; font-size: 12pt;">EP 657448 </span></li>
</ol>
</div>
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;"><script type="text/javascript"><br />ch_client = "sanalpcp";<br />ch_width = 500;<br />ch_height = 250;<br />ch_type = "mpu";<br />ch_sid = "Chitika Default";<br />ch_color_site_link = "0000CC";<br />ch_color_title = "0000CC";<br />ch_color_border = "FFFFFF";<br />ch_color_text = "000000";<br />ch_color_bg = "FFFFFF";<br /></script><br /><script src="http://scripts.chitika.net/eminimalls/amm.js" type="text/javascript"><br /></script></span><div>
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Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-75029390988117099872012-05-16T05:06:00.001-07:002012-05-16T05:06:27.730-07:00Laboratory Synthesis Of Famotidine<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="font-family: Arial,Helvetica,sans-serif; text-align: center;">
<u><b>Famotidine Synthesis</b></u></div>
<div style="font-family: Arial,Helvetica,sans-serif; text-align: center;">
<br /></div>
<div style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
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Use: ulcer therapeutic, H2-receptor antagonist</div>
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<br /></div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
<br /></div>
<br /><div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
<br /></div>
<div style="text-align: justify;">
<span style="font-family: Arial,Helvetica,sans-serif; font-size: 11pt; line-height: 115%;">The reaction ot
S-(2-aminothiazol-4-ylmethyl)isothiourea (I) with 3-chloropropionitrile (II) by
means of NaOH in ethanol - water gives
3-(2-aminothiazol-4-ylmethylthio)propionitrile (III), which is condensed with
benzoyl isothiocyanate (IV) in refluxing acetone to afford
3-[2-(3-benzoylthioureido)thiazol-4-ylmethylthio]propionitrile (V). The
hydrolysis of (V) with K2CO3 in acetone - methanol - water yields
3-(2-thioureidothiazonl-4-ylmethylthio)propionitrile (VI), which by methylation
with methyl iodide in refluxing ethanol is converted into
3-[2-(S-methylisothioureido)thiazol-4-ylmethylthio]propionitrile hydroiodide
(VII). The reaction of (VII) with NH3 and NH4Cl in methanol at 90 C in a
pressure vessel affords 3-(2-guanidinothiazol-4-ylmethylthio)propionitrile
(VIII), which by partial alcoholysis with methanol by means of dry HCl in CHCl3
is converted into methyl 3-(2-guanidinothiazol-4-ylmethylthio)propionimidate
(IX). Finally, this compound is treated with sulfamide in refluxing methanol.</span></div>
<div style="text-align: justify;">
<span style="font-family: Arial,Helvetica,sans-serif; font-size: 11pt; line-height: 115%;"> </span></div>
<div style="text-align: justify;">
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
<b style="mso-bidi-font-weight: normal;"><u>SYNTHESIS
REFERENCE</u></b></div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
Drugs Fut 1983, 8, 1, 14</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
US 4283408</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
DOS 2 951 675 (Yamanouchi; appl.
21.12.1979; J-prior. 2.8.1979).</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
DOS 3 008 056 (Yamanouchi; appl.
3.3.1980; J-prior. 6.3.1979, 23.6.1979).</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
GB 2 052 478 (Yamanouchi; appl.
6.3.1980; J-prior. 6.3.1979, 23.6.1979).</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
GB 2 055 800 (Yamanouchi; appl.
20.12.1979; J-prior. 2.8.1979).</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
<i>synthesis of S</i>-[2-aminothiazol-4-ylmethyl]isothiourea:</div>
<div class="MsoNormal" style="font-family: Arial,Helvetica,sans-serif; line-height: normal; margin-bottom: 0.0001pt; text-align: justify;">
Spragne, J.M.; Lund, A.H.; Ziegler,
C.: J. Am. Chem. Soc. (JACSAT) <b>68</b>, 2155 (1946).</div>
<span style="font-family: Arial,Helvetica,sans-serif; font-size: 11pt; line-height: 115%;"> </span></div>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com3tag:blogger.com,1999:blog-3483751417218006682.post-75180513157297801432012-05-15T18:40:00.000-07:002012-10-17T07:07:02.320-07:00Laboratory Synthesis Of Fenclofenac<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="text-align: center;">
<b><u>Fenclofenac Synthesis</u></b></div>
<div style="text-align: center;">
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The
reaction of 2,4-dichlorophenol with 2-chloroacetophenone<span style="mso-spacerun: yes;"> </span>by means of a copper catalyst and sodium
hydroxide gives 2-(2,4-dichlorophenoxy)acetophenone , which is treated with
sulfur in refluxing morpholine yielding
2-(2,4-dichlorophenoxy)phenylthioacetomorpholide . Finally this compound is
hydrolyzed with KOH in refluxing methanol</div>
<br />
<b><u>SYNTHESIS
REFERENCE</u></b><br />
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<span style="font-family: "Times New Roman","serif"; font-size: 12.0pt; line-height: 115%;">Click here to see the
US patent—<a href="http://www.google.com/patents/US3766263" target="_blank">CLICK HERE</a></span></div>
<br />
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<br />
<ol style="text-align: left;">
<li>DE 2 117 826 (Reckitt & Colman; appl. 13.4.1971; GB-prior.
14.4.1970).</li>
<li>GB 1 308 327 (Reckitt & Colman; valid from 19.4.1971;
prior. 14.4.1970).</li>
<li>US 3 766 263 (Reckitt & Colman; 16.10.1973; GB-prior.
14.4.1970).</li>
<li>Drugs Fut1977, 2, (10):665</li>
<li><span style="font-family: Times,"Times New Roman",serif; font-size: 11pt; line-height: 115%;">FR 2092044</span></li>
</ol>
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Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-70590711167228100982012-05-13T02:37:00.001-07:002012-05-13T02:37:38.682-07:00Laboratory Synthesis Of Cetirizine<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="text-align: center;">
<u><b>Cetirizine Synthesis</b></u></div>
Use: non-sedative antihistaminic<br />
<br />
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<div style="text-align: left;">
<u><b> Reference </b></u></div>
<div style="text-align: left;">
EP 58146 (patent)</div>
<div style="text-align: center;">
Synthesis of Levocetirizine</div>
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The reaction of racemic cetiricine (I) with SOCl2 in toluene gives the
acyl chloride (II), which is treated with ammonia to yield the
corresponding racemic amide (III). The optical resolution of (III) by
preparative chiral chromatography on a Chiralpak AD column affords the
(R)-isomer (IV), which is treated with HCl in refluxing methanol to
provide the chiral methyl ester (V). Finally, ester (V) is hydrolyzed
with aqueous HCl to provide the chiral target compound. The hydrolysis
of amide (IV) is not performed directly to the target acid owing to
purification problems (separation of the ammonium chloride formed in the
hydrolysis with HCl).</div>
<div style="text-align: justify;">
<u><b>Synthesis References</b></u></div>
<ol style="text-align: left;">
<li>Pflum, D.A.; et al.; A large-scale
synthesis of enantiomerically pure cetirizine dihydrochloride using
preparative chiral HPLC. Org Process Res Dev 2001, 5, 2, 110</li>
<li>GB 2225321 (patent)</li>
<li>EP 0617028 (patent)</li>
</ol>
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</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-83164132924741440292012-05-12T21:41:00.000-07:002012-05-12T21:41:13.332-07:00Laboratory Synthesis Of Carvedilol<div dir="ltr" style="text-align: left;" trbidi="on">
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<b><u>Carvedilol Synthesis</u> </b></div>
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Use: non-selective b1-adrenoceptor blocker with vasodilating activity<br />MW: 406.48 <br />MF: C24H26N2O4<br />LD50: 364 mg/kg (M, i.p.); 27 mg/kg (M, i.v.);<br /> 769 mg/kg (R, i.p.); 25 mg/kg (R, i.v.);<br /> >1 g/kg (dog, p.o.)</div>
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<img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi7ePO9JVnxACPYfBHnF0V_okugvrzzhOeaYSaQTjv_UdXMVrwFNlbNrgqLk64GXryRnTSiUlAzEiOT4JvGyzajgVI_EGiOBBPThalC99lh7lo8YafX2sXO_eQ_6hbT_shOGQUkmd6JyGJ9/s1600/synthesis+of+Carvedilol.TIF" /> </div>
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<u><b>Synthesis References</b></u></div>
<ol style="text-align: left;">
<li>Drugs Fut1983,8,(10):841</li>
<li>DE 2815926; EP 0004920; ES 479396; JP 54157558; US 4503067</li>
<li>EP 0918055</li>
</ol>
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</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com1tag:blogger.com,1999:blog-3483751417218006682.post-39564805507949412352012-05-12T03:21:00.001-07:002012-05-12T03:35:50.310-07:00GPAT M.Pharm Admission 2012<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="text-align: center;">
<div style="text-align: center;">
<b style="color: blue;">M.Pharm Admission India -2012 </b></div>
<b><span style="color: red;"></span></b></div>
<ol style="text-align: justify;">
</ol>
<ul style="font-family: Arial,Helvetica,sans-serif; text-align: left;">
<li><b><span style="color: red;">Tamilnadu Private Professional Colleges Association - Health Sciences (TNPPCAHS) Tamil Nadu M.Pharm Admission</span></b></li>
</ul>
<ol style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
</ol>
<div style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
<b>Important Dates:</b></div>
<div style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
Last date for receipt of filled application is <b>May 18, 2012</b>.</div>
<div style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
Entrance examination will be held on <b>May 27, 2012 at 10.00 AM to 11.30 AM</b>. <b></b></div>
<div style="text-align: justify;">
<div style="font-family: Arial,Helvetica,sans-serif;">
<b>for application and prospectus <a href="http://www.tnppcahs.org/application-mpharm.pdf" target="_blank">click here</a></b></div>
<ul style="font-family: Arial,Helvetica,sans-serif;">
<li><b><span style="color: red;">BITS Pilani , M.Pharm Admission 2012 </span></b><span style="color: #333333; font-size: 10pt;"> </span></li>
</ul>
<span style="color: #333333; font-family: Arial,Helvetica,sans-serif; font-size: 10pt;">Admissions to <b>M.E./M.Pharm </b>are based on performance of candidates in
<b>computer-based online test </b>conducted by BITS. The online tests will be
held during 3rd – 4th June 2012 at centers in India.</span><b style="font-family: Arial,Helvetica,sans-serif;"><span style="color: red;"> </span></b></div>
<div style="font-family: Arial,Helvetica,sans-serif; text-align: justify;">
<span style="font-size: 10pt;">Deadline for submission of the
Applications:
</span><span style="font-family: Helvetica; font-size: 10pt;"><b>5.00 P.M. on 23<sup>rd</sup> May
2012</b>.</span><span style="font-size: 10pt;"><b></b></span><br />
<span style="font-family: Helvetica; font-size: 10pt;">Online
Tests <b>
3<sup>rd</sup> – 4<sup>th</sup> June.2012</b></span><span style="font-size: 10pt;"><b> </b></span><br />
<span style="font-family: Helvetica; font-size: 10pt;">Announcement results
<b> 9<sup>th</sup> June.2012</b></span><br />
<span style="font-family: Helvetica; font-size: 10pt;"><b> </b></span><b>for application and prospectus <a href="http://www.bitsadmission.com/hd/BITSHDAPPLY/onlinereg.asp" target="_blank">click here</a></b><br />
</div>
<div style="text-align: justify;">
<b><b><span style="font-weight: normal;">tags:colleges admission through GPAT score,GPAT eligible M.pharm,M.Pharm thru GPAT 2012,M.Pharm admission india GPAT,list of pharmacy college accepts GPAT score, </span></b></b></div>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-7940703737058920872012-05-09T21:47:00.001-07:002012-05-09T21:47:23.475-07:00Laboratory Synthesis Of Apricoxib<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="text-align: center;">
<u><strong>Apricoxib synthesis</strong></u> </div>
<div style="text-align: center;">
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<b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">C19H20N2O3S</span></b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;"><o:p></o:p></span></div>
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<b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Mol
wt: 356.439</span></b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;"><o:p></o:p></span></div>
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<b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">CAS:
197904-84-0</span></b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;"><o:p></o:p></span></div>
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<b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">EN:
280412</span></b><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;"><o:p></o:p></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgidTfn3yOt3OtKbP2GXsvj93ln-tnwOBmnlLhMOpGm4DFLZ4KFSnkBl28LX-w5kd11eblNtajzetw550EOzzirJJWTd3SAtmYl8Oa_yQFXFG6qY5u6QgbijzJa3tvzM3En8DPSS0Nf6mMK/s1600/synthesis+of+Apricoxib.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgidTfn3yOt3OtKbP2GXsvj93ln-tnwOBmnlLhMOpGm4DFLZ4KFSnkBl28LX-w5kd11eblNtajzetw550EOzzirJJWTd3SAtmYl8Oa_yQFXFG6qY5u6QgbijzJa3tvzM3En8DPSS0Nf6mMK/s640/synthesis+of+Apricoxib.gif" width="632" /></a></div>
<div style="text-align: center;">
<strong><u>method of synthesis</u></strong></div>
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<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">In one strategy,
bromination of 4-ethoxyacetophenone (I) with Br2 yields
2-bromo-1-(4-ethoxyphenyl)ethanone (II) along with the byproduct
2-bromo-1-(3-bromo-4-ethoxyphenyl)ethanone, which are separated using HPLC.
Alkylation of propionaldehyde <i>N,N</i>diisobutylenamine (III) with bromo
ketone (II) and subsequent ketalization with neopentyl glycol (IV) using <i>p</i>-TsOH·H2O
and, optionally, H2SO4 in MeCN gives monoprotected ketoaldehyde (V) (1).
Finally, cyclization of ketoaldehyde derivative (V) with 4-aminobenzenesulfonamide
(VI) in the presence of AcOH in PrOH/H2O at 90-100 °C furnishes apricoxib <o:p></o:p></span></div>
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<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Intermediate (V)
can also be prepared by reaction of 1-(4- ethoxyphenyl)-2-buten-1-one (VII)
with CH3NO2 in the presence of DBU in THF to produce nitro ketone (VIII).
Subsequent treatment of nitro derivative (VIII) with neopentyl glycol (IV) and
NaOMe and MeOH gives acetal (V) (2).In an alternative strategy, condensation of
4-ethoxyacetaldehyde (IX) with 4-sulfamoylaniline (VI) in refluxing EtOH
furnishes <i>N</i>-(4-ethoxybenzylidene)-<o:p></o:p></span></div>
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<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">4-sulfamoylaniline
(X), which then condenses with trimethylsilyl cyanide (XI) in the presence of
ZnCl2 in THF yielding </span><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: SymbolMT;">α</span><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">-
amino nitrile (XII). Cyclization of this compound with methacrolein (XIII) using
LiHMDS in THF affords apricoxib </span></div>
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<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;"><strong><u>reference</u></strong></span></div>
<ol style="text-align: left;"><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">
<li><div class="MsoNormal" style="margin: 0cm 0cm 0pt; mso-layout-grid-align: none; text-align: justify;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Drugs of the
Future 2011, 36(7): 503-509<o:p></o:p></span></div>
</li>
<li><div class="MsoNormal" style="margin: 0cm 0cm 0pt; mso-layout-grid-align: none; text-align: justify;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Kojima, S., Ooyama, J. (Daiichi
Sankyo Co., Ltd.). Process for production of brominated acetophenone. WO
2008020617.<o:p></o:p></span></div>
</li>
<li><div class="MsoNormal" style="margin: 0cm 0cm 0pt; mso-layout-grid-align: none; text-align: justify;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Fujimoto, K., Takebayashi, T.,
Noguchi, Y., Saitou, T. (Daiichi Sankyo Co., Ltd.). Production of
4-methyl-1,2-diarylpyrrole and intermediate for synthesizing the same. JP
2000080078<o:p></o:p></span></div>
</li>
<li><div class="MsoNormal" style="margin: 0cm 0cm 0pt; mso-layout-grid-align: none; text-align: justify;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt;">Kimura, T., Noguchi, Y., Nakao,
A., Suzuki, K., Ushiyama, S., Kawara, A., Miyamoto, M. (Daiichi Sankyo Co.,
Ltd.). 1,2-Diphenylpyrrole derivatives,their preparation and their therapeutic
uses. CA 2201812, EP 0799823, JP 1997823971, US 5908858.<o:p></o:p></span></div>
</li>
</span></ol>
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</div>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-8684202066188817282012-05-09T21:28:00.000-07:002012-05-12T01:31:56.398-07:00Laboratory Synthesis Of Carprofen<div dir="ltr" style="text-align: left;" trbidi="on">
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<b><u>Carprofen Synthesis</u></b> </div>
<span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;">Use: non-steroidal anti-inflammatory<br />
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<span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;">MW: 273.72</span></span></span></div>
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<span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;">LD <span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;">50</span></span><span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;">: 400 mg/kg (M, p.o.)</span></span></span></span></div>
<span style="font-family: Arial; font-size: small;"><div style="text-align: center;">
<u>method of synthesis</u></div>
</span></span><div style="text-align: justify;">
<span style="font-family: Arial; font-size: small;"><span style="font-family: "Calibri","sans-serif"; font-size: 11pt; line-height: 115%;">cyclohexenone
(I) is condensed with diethyl methyl malonate (II) gives diethyl -methyl-(3-oxocyclohexanyl)malonate
(III) which is hydrolyzed and decarboxylated with refluxing dioxane-HCl to
yield alpha-methyl-3-oxocyclohexaneacetic acid (IV), oil, b.p.(0.7) = 164-6 C,
n(20)(D) = 1.4794. The condensation of (IV) with 4-chlorophenylhydrazine (A) in
acetic acid-water atfords 6-chloro-alpha-methyl-1,2,3,4-tetrahydrocarbazole-2-acetic
acid (V), which is esterified with ethanol-HCl to ethyl
6-chloro-alpha-methyl-1,2,3,4-tetrahydrocarbazole-2-acetate (VI) and aromatized
with chloranil (B) in refluxing xylene to give ethyl
6-chloro-alpha-methylcarbazole-2-acetate (VII)Finally, this ester is hydrolyzed
with NaOH in refluxing ethanol</span></span><br /><span style="font-family: Arial; font-size: small;">
</span></div>
<span style="font-family: Arial; font-size: small;"><div style="text-align: center;">
<span style="font-family: "Calibri","sans-serif"; font-size: 11pt; line-height: 115%;"><u><b>reference</b></u></span></div>
<ul style="text-align: left;">
<li>Drugs Fut1977,2,(1):15</li>
<li>US patent 3896145</li>
</ul>
<span style="font-family: Arial; font-size: small;"><span style="font-family: Arial; font-size: small;"></span></span></span><br />
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</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-33832789330710054932012-05-09T20:51:00.000-07:002012-05-09T20:51:00.445-07:00Laboratory Synthesis Of Benazepril<div dir="ltr" style="text-align: left;" trbidi="on">
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<strong><u>Benazepril Synthesis</u></strong> </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgKqkwdb9hVWA6begaXAwA124hvWSTg6CkT2KxdTbZf63oLni-k6pzmArYPRHh_EV0wBeDql4T3ZWnjsvoiB9PbhbQXUWmNABaRB42Rly4xNVtQ6F1htVSziEJnxva3ORPfWvKgxkcuzxv2/s1600/Benazepril+synthesis.tif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgKqkwdb9hVWA6begaXAwA124hvWSTg6CkT2KxdTbZf63oLni-k6pzmArYPRHh_EV0wBeDql4T3ZWnjsvoiB9PbhbQXUWmNABaRB42Rly4xNVtQ6F1htVSziEJnxva3ORPfWvKgxkcuzxv2/s1600/Benazepril+synthesis.tif" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqvPTUmIwhi0doiXVXweaLUSYZB6MgFwDdRKOnZ7o-mYLtLrvsAFDk5ls1VKuYDIm5WBI_N2kFpqNhJ8hLn29pemZ96tW1_lmVkIly-bDmEin-xkhK10F749wli_KeAjoIvQrYdD1WgX3E/s1600/Benazepril+synthesis-1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqvPTUmIwhi0doiXVXweaLUSYZB6MgFwDdRKOnZ7o-mYLtLrvsAFDk5ls1VKuYDIm5WBI_N2kFpqNhJ8hLn29pemZ96tW1_lmVkIly-bDmEin-xkhK10F749wli_KeAjoIvQrYdD1WgX3E/s1600/Benazepril+synthesis-1.jpg" /></a></div>
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The reaction of 2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (I) with PCl5 in hot xylene gives 3,3-dichloro-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (II), which is treated with sodium acetate and reduced with H2 over Pd/C in acetic acid yielding 3-chloro-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (III). The reaction of (III) with sodium azide in DMSO affords 3-azido-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (IV), which is condensed with benzyl bromoacetate (V) by means of NaH in DMF giving 3-azido-1-(benzyloxycarbonylmethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VI). The treatment of (VI) with Raney-Ni in ethanol-water yields 3-amino-1-(benzyloxycarbonylmethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VII), which is debenzylated by hydrogenation with H2 over Pd/C in ethanol affording 3-amino-1-(carboxymethyl)-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VIII). Finally, this compound is condensed with ethyl 3-benzylpyruvate (IX) by means of sodium cyanoborohydride in methanol acetic acid.<a href="http://www.chemdrug.com/"><img src="http://www.chemdrug.com/images/space.gif" /></a></div>
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<u>REFERENCE</u></div>
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Casta馿r, J.; Serradell, M.N.; CGS-14824 A. Drugs Fut 1984, 9, 5, 317</div>
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Ciba-Geigy Corp. (USA). References 1. Watthey, J.W.H. (Ciba-Geigy AG); EP 72.352, GB 2.103.614, JP 83.38.260.</div>
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J Label Compd Radiopharm1987,24,(10):1177-84</div>
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The reaction of 3-bromo-1-phenylpropane (I) with KCN gives 4-phenylbutyronitrile (II), which is hydrolyzed to the corresponding butyric acid (III). The cyclization of (III) with polyphosphoric acid affords 1-tetralone (IV), which is brominated to 2-bromo-1-tetralone (V) and treated with hydroxylamine to give the oxime (VI). The Beckman rearrangement of (VI) yields 3-bromo-2,3,4,5-tetrahydro-1H-(1)benzazepin-2-one (VII), which is treated with sodium azide to afford the azide derivative (VIII). The N-alkylation of (VIII) with ethyl bromoacetate (IX) by means of KOH and tetrabutylammonium bromide in THF gives the N-alkylated azide (X), which is reduced by catalytic hydrogenation to the corresponding amine (XI). The hydrolysis of the ester group of (XI) with NaOH yields the free acetic acid derivative (XII), which is finally reductocondensed with ethyl 2-oxo-4-phenylbutyrate (XIII) by means of sodium cyanoborohydride.<a href="http://www.chemdrug.com/"><img src="http://www.chemdrug.com/images/space.gif" /></a></div>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-47718369964899527872012-05-09T06:12:00.002-07:002012-05-09T06:12:26.716-07:00Laboratory Synthesis Of Ranitidine<div dir="ltr" style="text-align: left;" trbidi="on">
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Synthesis Of Ranitidine</div>
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<strong><u>Ranitidine Synthetic procedure/method of synthesis</u></strong><br />
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The reaction of 5-dimethylaminomethyl-2-furanylmethanol (I) with 2-mercaptoethylamine (II) by means of aqueous HCl gives 2-[[(5-dimethylamino-methyl-2-furanyl)methylthio]ethaneamine (III), which is then condensed with N-methyl-1-methylthio-2-nitrotheneamine (IV) by heating at 120 C. Compound (IV) is obtained by reaction of 1,1-bis(methylthio)-2-nitroethene (V) with methylamine in refluxing ethanol</div>
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<strong><u>Ranitidine reference</u></strong></div>
<ol style="text-align: left;">
<li><div style="text-align: left;">
Serradell, M.N.; Blancafort, P.; Casta馿r, J.; Hillier, K.; Ranitidine. Drugs Fut 1979, 4, 9, 663</div>
</li>
<li><div style="text-align: left;">
Price, B.J. et al. (Allen and Hanburys, Ltd.); US 4128658.</div>
</li>
<li><div style="text-align: left;">
Price, B.J.; Bradshaw, J.; Clitherow, J.W. (Allen & Hansburys Ltd.); Aminoalkyl furan derivatives.. DE 2734070; FR 2360587; US 4128658 ,DE 2734070; FR 2360587; US 4128658.</div>
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</ol>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com1tag:blogger.com,1999:blog-3483751417218006682.post-63901169056687758862012-05-01T21:29:00.000-07:002012-05-01T21:29:49.362-07:00Laboratory Synthesis Of Nicotine<div dir="ltr" style="text-align: left;" trbidi="on">
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SYNTHESIS OF NICOTINE</div>
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TAGS-laborotory synthesis of nicotine,tobacco alkaloid synthesis,preparation of nicotine</div>
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</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-5502023172138403812012-04-29T21:26:00.000-07:002012-05-02T21:02:04.118-07:00Laboratory Synthesis Of Clofibrate<div dir="ltr" style="text-align: left;" trbidi="on">
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CLOFIBRATE SYNTHESIS</div>
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<br />
<u>References</u></div>
<div class="MsoListParagraphCxSpFirst" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-align: left; text-indent: -18pt;">
<span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">1.<span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Jones <i>et al.,</i> <b>GB</b>
<b>860303</b> (1961 to I.C.I.).<o:p></o:p></span></div>
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</div>
<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-align: left; text-indent: -18pt;">
<span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">2.<span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Prepn: Galimberti,
Defranceschi, <i>Gazz. Chim. Ital.</i> <b>77,</b> 431 (1947); <o:p></o:p></span></div>
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</div>
<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-align: left; text-indent: -18pt;">
<span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">3.<span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Gilman, Wilder, <i>J. Am.
Chem. Soc.</i> <b>77,</b> 6644 (1955);<o:p></o:p></span></div>
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</div>
<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-align: left; text-indent: -18pt;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">4.<span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";"> </span></span></span><span style="color: black; font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">Prepn and resolution of isomers: Witiak <i>et al.,</i> <i>J. Med.
Chem.</i> <b>11,</b> 1086</span><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;"><o:p></o:p></span></div>
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<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-align: left; text-indent: -18pt;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">5.<span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";"> </span></span></span><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">US
patent 4739101 <o:p></o:p></span></div>
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</div>
<div class="MsoListParagraphCxSpLast" style="margin: 0cm 0cm 10pt 36pt; mso-list: l0 level1 lfo1; text-align: left; text-indent: -18pt;">
<span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">6.<span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";"> </span></span></span><span style="font-family: "Times New Roman","serif"; font-size: 12pt; line-height: 115%;">US
patent 3262850<o:p></o:p></span></div>
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</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com3tag:blogger.com,1999:blog-3483751417218006682.post-38600890540846606962012-04-28T21:15:00.001-07:002012-04-29T20:27:50.556-07:00Laboratory Synthesis Of Minoxidil<div dir="ltr" style="text-align: left;" trbidi="on">
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Synthesis Of Minoxidil</div>
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It can be prepared by two different methods both of them are starting from 2,4-diamino-6-chloropyrimidine (I): 1) The oxidation of (I) with m-chloroperbenzoic acid (MCPBA) gives 6-amino-4-chloro-1,2-dihydro-1-hydroxy-2-iminopyrimidine (II), which is then condensed with piperidine. 2) A mixture of (I), 2,4-dichlorophenol (A) and KOH was heated at 150 C to give 2,4-diamino-6-(2,4-dichlorophenoxy)pyrimidine (III), which is oxidized with m-chloroperbenzoic acid (MCPBA) in alcohol giving 6-amino-4-(2,4-dichlorophenoxy)-1,2-dihydro-1-hydroxy-2-iminopyrimidine (IV). Finally, this product is treated with piperidine at 150 C.<img src="http://www.chemdrug.com/images/space.gif" />to afford the target compound minoxidil.</div>
<div style="text-align: justify;">
<br /></div>
<div style="text-align: justify;">
<u>REFERENCE</u></div>
<ol style="text-align: left;">
<li><div style="text-align: justify;">
Anthony, W.C.; et al.; 6-Amino-1,2-dihydro-1-hydroxy-2-imino-4-phenoxypyrimidines. CH 495361; DE 1795837; FR 1510017; GB 1167736; US 3382247; US 3382248; US 3461461 </div>
</li>
<li><div style="text-align: justify;">
Hyde, T.J.; N-Alkyl pyrrolidone-plasticized copolylactam compositions. US 3644264 </div>
</li>
</ol>
<div style="text-align: justify;">
tags-synthesis of Minoxidil, TM-160, U-10858, Minoximen, Neoxidil, RiUP, Loniten, Rogaine, Regaine,how to synthesize minoxidil</div>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com1tag:blogger.com,1999:blog-3483751417218006682.post-70324715834621615042012-04-27T20:25:00.000-07:002012-04-28T04:19:08.417-07:00Laboratory Synthesis Of Idarubicin<div dir="ltr" style="text-align: left;" trbidi="on">
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COMPLETE SYNTHESIS OF IDARUBICIN </div>
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condensation of chiral tetraline (I) with phthalic anhydride (II) by means of AlCl3 at 180 C gives the naphthacenedione (III), acetyl group which is ketalized with ethylene glycol and p-toluenesulfonic acid yielding the dioxolane (IV). The hydroxylation of (IV) with Br2 and AIBN in CCl4/CHCl3 affords the 4-demethoxy-7-epidaunomycinone (V), which is isomerized with TFA yielding 4-demethoxydaunomycinone (VI) . The condensation of (VI) with the acylated hexopyranosyl chloride (VII) by means of CF3SO3Ag of Br2Hg affords the trifluoroacetylated 4-demethoxydaunomycin (VIII), which is finally deprotected by treated with NaOH to eliminate the trifluoroacetyl groups<a href="http://www.chemdrug.com/"><img src="http://www.chemdrug.com/images/space.gif" /></a></div>
<div style="text-align: justify;">
<u><strong>Reference</strong></u></div>
<ol style="text-align: left;">
<li><div style="text-align: justify;">
Arcamone, F.; et al.; Synthesis and antitumour activity of new daunorubicin and adriamycin analogues. Experientia 1978, 34, 1255</div>
</li>
<li><div style="text-align: justify;">
Bernardi, L.; Arcamone, F.; Patelli, B.; Di Marco, A. (Pharmacia Corp.); Daunomycin analogues, their preparation and use. DE 2525633; US 4046878 </div>
</li>
</ol>
tags-synthesis of NSC-256439, IMI-30, DMDR, Idamycin, Zavedos,HOW IDARUBICIN IS SYNTHESIZED</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-53301144565129758332012-04-26T21:02:00.000-07:002012-04-26T21:02:23.431-07:00Laboratory Synthesis Of Ramipril<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="text-align: center;">
<u>Complete Synthesis of Ramipril</u></div>
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<u>Reference </u></div>
<ol style="text-align: left;">
<li><div style="text-align: justify;">
Mannhold, R.; Serradell, M.N.; Casta馿r, J.; Ramipril. Drugs Fut 1985, 10, 5, 400</div>
</li>
<li><div style="text-align: justify;">
Teetz, V.; et al. (Aventis Pharma AG); Method for making 2-azabicyclo[3.3.0]octane-3-carboxylic acids. DE 3226768; EP 0079022; EP 0150263; JP 2104526; JP 2104573; JP 4217949; US 4727160; US 5053519 </div>
</li>
</ol>
</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-4605986428295415232012-03-04T07:07:00.000-08:002012-03-04T07:07:51.957-08:00Synthesis Of Aceclofenac<div dir="ltr" style="text-align: left;" trbidi="on"><table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="margin-left: auto; margin-right: auto; text-align: center;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhaLR4OYW64tpTmRIiIOiPc-Rj9kyYPsZ65kDNv-bZ64_CHm3k3Yrtumev1H_qvqbSevE7tifwLCEWkh4gHDIoRuv6xjNRRebyN4bFqoDH6MDyHIBKb6cm4MTGep8-w7X8L8VfjsOi9IDxv/s1600/Laboratory+Synthesis+Of+Aceclofenac.gif" style="margin-left: auto; margin-right: auto;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhaLR4OYW64tpTmRIiIOiPc-Rj9kyYPsZ65kDNv-bZ64_CHm3k3Yrtumev1H_qvqbSevE7tifwLCEWkh4gHDIoRuv6xjNRRebyN4bFqoDH6MDyHIBKb6cm4MTGep8-w7X8L8VfjsOi9IDxv/s1600/Laboratory+Synthesis+Of+Aceclofenac.gif" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">synthesis of aceclofenac</td></tr>
</tbody></table>Aceclofenac Chemical Name IUPAC : [[[2- [(2 ,6- di chloro phenyl )amino ]phenyl ]acetyl ]oxy ]acetic acid<br />
Aceclofenac Use: non-steroidal anti-inflammatory, analgesic,antipyretic, prostaglandin synthesis inhibitor<br />
Aceclofenac MW: 354.19 MF: C16H13Cl2NO4<br />
Aceclofenac LD50: 121 mg/kg (M, p.o.)<br />
<br />
<div class="cAO"><div class="cAP" id="CLK0008P0005">A white to almost white crystalline powder. Aceclofenac M.p. 149° to 150°.<br />
Aceclofenac solubility: It is practically insoluble in water; soluble in alcohol and methyl alcohol; freely soluble in acetone and dimethylformamide. </div></div><div class="cAO" id="CLK0008P0010"><h2 class="cAW">Thin–layer Chromatography.</h2><div class="cAW">Plate: silica gel. Mobile phase: chloroform:methanol:acetic acid (90:10:1). Aceclofenac, Rf 0.44; 4′-OH aceclofenac, Rf 0.25. [R. Bort <i>et al</i>.,<i>Drug Metab. Dispos.</i>,1996, <b>24</b>8, 834–841]. </div></div><div class="cAO" id="CLK0008P0015"><h2 class="cAW">High Performance Liquid Chromatography.</h2><div class="cAW">System HZ—retention time 10.7 min. </div><div class="cAW">Column: C<sub>18</sub> (Spherisorb ODS–2, 5 μm, 200 × 4.6 mm). Mobile phase: triethanolamine (0.02% in 100 mM phosphate buffer, pH 7.4):acetonitrile (75:25), flow rate 1.0 mL/min. UV Detection (λ=282 nm). Retention time: aceclofenac, 23.4 min; 4′-hydroxyaceclofenac, 7.6 min. [R. Bort <i>et al</i>.,<i>Drug Metab. Dispos.</i>,1996, <b>24</b>8, 834–841]. </div></div><br />
<u>Reference(s):</u><br />
EP 119 932 (Prodes; appl. 19.3.1984; E-prior. 21.3.1983).<br />
US 4 548 952 (Prodes; 22.10.1985; appl. 15.3.1984; E-prior. 21.3.1983).<u> </u><br />
<u>Alternative synthesis:</u><br />
ES 2 020 146 (Prodesfarma; appl. 29.5.1990).<br />
<br />
tags-synthesis of drugs,method of preparation of Aceclofenac ,molecular weight Aceclofenac , molecular formula of Aceclofenac,structure of Aceclofenac</div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-56848682726127854002012-01-08T07:08:00.000-08:002012-01-08T07:09:44.832-08:00Laboratory Synthesis Of Bromazepam<div dir="ltr" style="text-align: left;" trbidi="on"><div style="text-align: center;"><u><b>Chemical Synthesis Of Bromazepam</b></u><br />
<div class="separator" style="clear: both;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgIRowBzQOUkAPtsqTkcPqTZicwFLRNIG6azI5LcPZ4q9D_N2xgd3Rs_yswHlAGYFuR-UQRz2COjj_cmtzieL2wNqmDHudSMDrvqexx_EDvsZNuIpT04v2u3-6zGhwFVdxJjJ_2aWNRowxd/s1600/Laboratory+Synthesis+Of+Bromazepam.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgIRowBzQOUkAPtsqTkcPqTZicwFLRNIG6azI5LcPZ4q9D_N2xgd3Rs_yswHlAGYFuR-UQRz2COjj_cmtzieL2wNqmDHudSMDrvqexx_EDvsZNuIpT04v2u3-6zGhwFVdxJjJ_2aWNRowxd/s1600/Laboratory+Synthesis+Of+Bromazepam.gif" /></a></div><div style="text-align: left;">BromazepamUse: tranquilizer</div><div style="text-align: left;">Bromazepam CN: 7- bromo- 1 ,3- di hydro- 5- (2- pyridinyl)- 2 H- 1 ,4- benzo diazepine- 2- one </div><div style="text-align: left;">Bromazepam MW: 316.16 MF: C14H10BrN3O</div><div style="text-align: left;">Bromazepam LD50: 879 mg/kg (M, p.o.);1950 mg/kg (R, p.o.)<u><b><br />
Bromazepam Reference(s):</b></u>a US 3 100 770 (Roche; 13.8.1963; appl. 11.8.1961).</div><div style="text-align: left;">US 3 182 065 (Roche; 4.5.1965; appl. 9.4.1964; prior. 19.4.1963).</div><div style="text-align: left;">US 3 182 066 (Roche; 4.5.1965; appl. 9.4.1964; prior. 19.4.1963).</div><div style="text-align: left;">US 3 182 067 (Roche; 4.5.1965; appl. 9.4.1964).</div><div style="text-align: left;">Fryer, R.I. et al.: J. Pharm. Sci. (JPMSAE) 53, 264 (1964).</div><div style="text-align: left;"><u><b>modified methods:</b></u></div><div style="text-align: left;">DAS 2 233 483 (Roche; appl. 7.7.1972; GB-prior. 8.7.1971, 7.10.1971).</div><div style="text-align: left;">DOS 2 252 378 (Roche; appl. 25.10.1972; CH-prior. 18.11.1971).</div><div style="text-align: left;"><b><u>alternative synthesis of 2-(2-amino-5-bromobenzoyl)pyridine:</u></b></div><div style="text-align: left;">DAS 2 256 614 (Roche; appl. 17.11.1972).</div><div style="text-align: left;">b DAS 1 813 241 (Roche; appl. 6.12.1968; J-prior. 8.12.1967, 9.12.1967, 12.12.1967,</div><div style="text-align: left;">25.4.1968).</div><div style="text-align: left;"><u><b>combination with sulpiride:</b></u></div><div style="text-align: left;">DAS 2 342 214 (Roche; appl. 21.8.1973; CH-prior. 21.9.1972).</div><div style="text-align: left;"><u></u></div><div style="text-align: left;"><u></u></div><div style="text-align: left;"><u><b></b></u></div><div style="text-align: left;"><br />
</div><div class="cAO" style="text-align: left;"><div class="cAP" id="CLK0225P0005">A white or yellowish crystalline powder. M.p. 237° to 238.5° with decomposition. <br />
Practically insoluble in water, sparingly soluble in alcohol and in dichloromethane. </div></div><div class="cAO" id="CLK0225P0010" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Dissociation Constant.</span></h2><div class="cAW"><span style="font-size: small;">pK<sub>a</sub>2.9, 11.0.</span></div></div><div class="cAO" id="CLK0225P0015" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Partition Coefficient.</span></h2><div class="cAW"><span style="font-size: small;">Log <i>P</i>(octanol/water), 2.05.</span></div></div><div class="cAO" id="CLK0225P0020" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Colour Test.</span></h2><div class="cAW"><span style="font-size: small;">Formaldehyde–Sulfuric Acid—yellow. </span></div></div><div class="cAO" id="CLK0225P0025" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Thin–layer Chromatography.</span></h2><div class="cAW"><span style="font-size: small;">System TA—Rf 61; system TB—Rf 6; system TC—Rf 41; system TD—Rf 13; system TE—Rf 63; system TF—Rf 18; system TL—Rf 53; system TAD—Rf 47; system TAE—Rf 73; system TAF—Rf 69; system TAJ—Rf 34; system TAK—Rf 04; system TAL—Rf 63. </span></div></div><div class="cAO" id="CLK0225P0030" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Gas Chromatography.</span></h2><div class="cAW"><span style="font-size: small;">System GA—bromazepam RI 2665, M (3-OH-) RI 2470; system GB—bromazepam RI 2760, bromazepam-TMS RI 2702; M (3-OH-)-TMS<sub>2</sub> RI 2650; system GG—RI 3280. </span></div><div class="cAW"><span style="font-size: small;">Column: DB-17 (30 m × 0.32 mm i.d., 0.25 μm film thickness). Column temperature: 150°, held for 1 min, ramp to 230°, held for 5 min, ramp to 300° held for 9 min at 10°/min. Injector and detector temperatures: 270° and 300°, respectively. Carrier gas: helium (pre–column pressure, 80 kPa). Detection: ECD. Retention time: 18.0 min. [F. Guan et al.,<i>J. Anal. Toxicol.</i>,1999, <b>23</b>, 54–61.] </span></div><div class="cAW"><span style="font-size: small;">Column: HP5-MS (5% phenyl:95% siloxane, 30 m × 0.25 mm, 0.25 μm film thickness). Column temperature: 60° held for 1 min, ramp to 295° at 30°/min, held for 6 min. Injector temperature: 250°. Carrier gas: helium, flow rate 1 mL/min. MS detection (NCI mode). Retention time: 9.7 min. [P. Kintz et al.,<i>J. Chromatogr. B Biomed. Sci. Appl.</i>,1997, <b>700</b>, 119–129.] </span></div></div><div class="cAO" id="CLK0225P0035" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam High Performance Liquid Chromatography.</span></h2><div class="cAW"><span style="font-size: small;">System HI—k 2.32; system HK—k 2.99; system HX—RI 397; system HY—RI 331; system HZ—retention time 3.0 min; system HAA—retention time 14.7 min; system HAF—retention time 6.6 min (tailing peak); system HAX—retention time 5.8 min; system HAY—retention time 5.1 min; system HBH—k 1.63; system HBI—k 0.80; system HAL—retention time 8.1 min; system HAM—not detected. </span></div><div class="cAW"><span style="font-size: small;">Column: RP C<sub>18</sub> (150 × 3.9 mm i.d., 5 μm). Mobile phase: water:acetonitrile:triethylamine (700:300:4), adjusted to pH 7.4 with phosphoric acid, flow rate 2 mL/min. UV detection (λ = 240 nm). Retention time: bromazepam, 2.1 min, <i>α</i>-hydroxytriazolam (IS), 3.2 min. [Le Solleu et al.,<i>J. Pharm. Biomed. Anal.</i>,1993, <b>11</b>, 771–775.] </span></div></div><div class="cAO" id="CLK0225P0040" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Ultraviolet Spectrum.</span></h2><div class="cAW"><span style="font-size: small;">Aqueous acid—239, 345 nm; aqueous alkali—237 nm (A<sup>1</sup><sub>1</sub>=920b), 348 nm; methanol—233 nm (A<sup>1</sup><sub>1</sub>=1050b), 320 nm (A<sup>1</sup><sub>1</sub>=61b). </span></div><div class="cAN" id="CLK0225U001"> </div></div><div class="cAO" id="CLK0225P0045" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Infra–red Spectrum.</span></h2><div class="cAW"><span style="font-size: small;">Principal peaks at wavenumbers 1685, 825, 750, 802, 1315, 1230 cm<sup>−1</sup>. </span></div><div class="cAN" id="CLK0225I001"> </div></div><div class="cAO" id="CLK0225P0050" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Mass Spectrum.</span></h2><div class="cAW"><span style="font-size: small;">Principal ions at <i>m/z</i> 236, 317, 315, 288, 316, 286, 208, 78; 3–hydroxybromazepam 79, 78, 52, 105, 304, 314, 316, 51. </span></div><div class="cAN" id="CLK0225M001"> </div></div><div class="cAO" id="CLK0225P0055" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Quantification.</span></h2><div class="cAQ" id="CLK0225P0065"><h4 class="cAW"><span style="font-size: small;">Gas chromatography.</span></h4><div class="cAW"><span style="font-size: small;">In plasma: limit of detection 5 μg/L, ECD—U. Klotz,<i>J. Chromatogr.</i>,1981, <b>222(21) B Biomed. Appl.</b>, 501–506. In plasma or blood: bromazepam and other benzodiazepines, ECD and NPD—P. Lillsunde and T. Seppala,<i>J. Chromatogr.</i>,1990, <b>533</b>, 97–110. In hair: limit of detection, 20 pg/mg hair, MS (NCI mode)—P. Kintz et al.,<i>J. Chromatogr. B Biomed. Sci. Appl.</i>,1997, <b>700</b>, 119–129. In urine: bromazepam and other benzodiazepines, limit of detection for bromazepam 160 μg/L, ECD—F. Guan et al.,<i>J. Anal. Toxicol.</i>,1999, <b>23</b>, 54–61.</span></div></div><div class="cAQ" id="CLK0225P0070"><h4 class="cAW"><span style="font-size: small;">Bromazepam Gas chromatography–mass spectrometry.</span></h4><div class="cAW"><span style="font-size: small;">In tissue: limit of quantification, 50 ng/g tissue, SIM—X.X. Zhang et al.,<i>J. Chromatogr.</i>,1996, <b>677 B Biomed. Appl.</b>, 111–116. In urine: bromazepam, diazepam, and nordazepam, TOF–MS, comparison with MS and ECD—B. Aebi <i>et al</i>.,<i>Forensic Sci. Int.</i>,2002, <b>128</b>, 84–89.</span></div></div><div class="cAQ" id="CLK0225P0075"><h4 class="cAW"><span style="font-size: small;">Bromazepam High performance liquid chromatography.</span></h4><div class="cAW"><span style="font-size: small;">In plasma: limit of detection 5 μg/L, UV detection—H. Hirayama <i>et al</i>.,<i>J. Chromatogr.</i>,1983, <b>277(28) B Biomed. Appl.</b>, 414–418. In plasma: limit of detection 3 μg/L, UV detection—A. Boukhabza <i>et al</i>.,<i>Analyst</i>,1989, <b>114</b>, 639–641. In plasma: limit of detection, 50 μg/L, UV detection—H. Le Solleu et al.,<i>J. Pharm. Biomed. Anal.</i>,1993, <b>11</b>, 771–775. In serum: bromazepam and other benzodiazepines, UV detection—E. Tanaka <i>et al</i>.,<i>J. Chromatogr.</i>,1996, <b>682 B Biomed Appl.</b>, 173–178 and E. Tanaka <i>et al</i>.,<i>J. Chromatogr. B Biomed. Sci. Appl.</i>,1998, <b>709</b>, 324.</span></div></div></div><div class="cAO" id="CLK0225P0080" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Disposition in the Body.</span></h2><div class="cAW"><span style="font-size: small;">Well absorbed after oral administration and peak plasma concentrations are usually achieved within 2 h. About 70% of a dose is excreted in the urine in 72 h, including about 2% of the dose as unchanged bromazepam, about 27% as the glucuronide of 3–hydroxybromazepam, about 40% as the glucuronide of 2–amino–5–bromo–3–hydroxybenzoylpyridine, and less than 1% as 2-(2–amino–5–bromobenz–oyl)-pyridine.</span></div><div class="cAP" id="CLK0225P0085"><div class="cAQ" id="CLK0225P0090"><h4 class="cAW"><span style="font-size: small;">Bromazepam Therapeutic concentration</span></h4><span style="font-size: small;">After a single oral dose of 12 mg, administered to 10 subjects, peak plasma concentrations of 0.11 to 0.17 mg/L (mean 0.13) were attained in 1 to 4 h. Steady–state concentrations of 0.08 to 0.15 mg/L (mean 0.12) were measured during dosing of 6 subjects with 9 mg daily. [S. A. Kaplan <i>et al</i>.,<i>J. Pharmacokinet. Biopharm.</i>,1976, <b>4</b>, 1–16.]</span><br />
<span style="font-size: small;">Administration of bromazepam as a slow–release formulation to 24 healthy subjects after an overnight fast resulted in peak plasma concentrations of 9.09 to 13.00 μg/L (mean 11.05 μg/L) attained in 4 to 16 h (mean 8 h); the corresponding values for a conventional–release preparation administered as 2 separate 1.5 mg doses, 12 h apart, were 8.91 to 11.50 μg/L (mean 10.21 μg/L) in 2 to 8 h (mean 8 h). [F. E. Lerner <i>et al</i>.,<i>Arzneimittelforschung</i>,2001, <b>51</b>, 955–958.]</span></div><div class="cAQ" id="CLK0225P0095"><h4 class="cAW"><span style="font-size: small;">Toxicity</span></h4><span style="font-size: small;">In a 68–year–old woman who was found unconscious and barely breathing, bromazepam intoxication was discovered to be the cause (a serum level of 6 mg/L was detected); normal functions were restored 12 days after the ingestion. [J. Rudolf <i>et al</i>.,<i>Dtsch. Med. Wochenschr.</i>,1998, <b>123</b>, 832–834.]</span><br />
<span style="font-size: small;">A 42–year–old woman ingested 420 mg bromazepam in a suicide attempt and survived despite being found unconscious outdoors in a state of semi–undress and suffering from hypothermia. About 12 h after the ingestion the blood concentration of bromazepam was 7.7 mg/L. [K. Michaud <i>et al</i>.,<i>Forensic Sci. Int.</i>,2001, <b>124</b>, 112–114.]</span></div><div class="cAQ" id="CLK0225P0100"><h4 class="cAW"><span style="font-size: small;">Bromazepam Half–life.</span></h4><div class="cAW"><span style="font-size: small;">Plasma half–life, 8 to 19 h (mean 12).</span></div></div><div class="cAQ" id="CLK0225P0105"><h4 class="cAW"><span style="font-size: small;">Bromazepam Volume of distribution.</span></h4><div class="cAW"><span style="font-size: small;">About 0.9 L/kg.</span></div></div><div class="cAQ" id="CLK0225P0110"><h4 class="cAW"><span style="font-size: small;">Bromazepam Protein binding.</span></h4><div class="cAW"><span style="font-size: small;">In plasma, 70%.</span></div></div></div></div><div class="cAO" id="CLK0225P0115" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Bromazepam Dose.</span></h2><div class="cAW"><span style="font-size: small;">Usually 3 to 18 mg daily; up to a maximum of 60 mg daily in divided doses has been given to hospitalised patients.</span></div><div class="cAW"><b>tags</b>-synthesis of drugs,method of preparation of Bromazepam,molecular weight Bromazepam, molecular formula of Bromazepam,structure of Bromazepam,A1%1 cm<span style="font-size: small;"> Bromazepam</span></div></div></div></div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-18618158167945770512012-01-07T09:01:00.000-08:002012-01-07T09:02:19.047-08:00Laboratory Synthesis Of Benzatropine<div dir="ltr" style="text-align: left;" trbidi="on"><div style="text-align: center;"><u><b><span style="font-size: small;">Chemical Synthesis Of</span><span style="font-size: small;"> Benzatropine</span></b></u></div><div style="text-align: center;"><span style="font-size: small;"><br />
</span><br />
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJvjKXc4SMgsSUVUNMGyWfFqEi_HxsMoDQiacB-LS_RcQLlhRFTRbs4iQZR0Z7fEG_a5YwzFXT0FYpLbpb0QeBG6UHzy83w8neM30v17ba25ke4FQhc2NY6iEnnNhvhhyH-8A0FDxzpc4S/s1600/Chemical+Synthesis+Of+Benzatropine.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhJvjKXc4SMgsSUVUNMGyWfFqEi_HxsMoDQiacB-LS_RcQLlhRFTRbs4iQZR0Z7fEG_a5YwzFXT0FYpLbpb0QeBG6UHzy83w8neM30v17ba25ke4FQhc2NY6iEnnNhvhhyH-8A0FDxzpc4S/s1600/Chemical+Synthesis+Of+Benzatropine.gif" /></a></div><div style="text-align: left;"><span style="font-size: small;">Benzatropine Use: parasympatholytic, antiparkinsonian </span></div><div style="text-align: left;"><span style="font-size: small;">Benzatropine MW: 307.44</span></div><div style="text-align: left;"><span style="font-size: small;"> MF: C21H25NO<br />
LD50: 25 mg/kg (M, i.v.)<br />
CN: endo- 3- (di phenyl methoxy)- 8- methyl- 8- aza bi cyclo [3 .2 .1 ]octane </span></div><div style="text-align: left;"><span style="font-size: small;"><u><b>Benzatropine mesylate</b></u><br />
RN: 132-17-2 EINECS: 205-048-8<br />
MW: 403.54 </span></div><div style="text-align: left;"><span style="font-size: small;">MF: C21H25NO · CH4O3S<br />
LD50: 24 mg/kg (M, i.v.); 91 mg/kg (M, p.o.);940 mg/kg (R, p.o.)</span></div><div style="text-align: left;"><u><b>Reference(s):</b></u><br />
US 2 595 405 (Merck & Co.; 1952; prior. 1949).</div><div class="cAO" style="text-align: justify;"><div class="cAP" id="CLK0192P0001"><span style="font-size: small;">Benzatropine solubility :Soluble in chloroform. </span></div></div><div></div><div class="cAO" id="CLK0192P0005" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Mesilate</span></h2><div class="cAP" id="CLK0192P0010"><div class="cBG"><span style="font-size: small;"><i>Synonyms.</i> Benzatropine Methanesulfonate; Tropine Diphenylmethyl Ether.</span></div></div><div class="cAP" id="CLK0192P0015"><div class="cBG"><span style="font-size: small;"><i>Proprietary names.</i> Bensylate; Cogentin.</span></div><div class="cBG"><span style="font-size: small;"><span class="cBL">C<sub>21</sub>H<sub>25</sub>NO,CH<sub>4</sub>O<sub>3</sub>S</span>=<span class="cBM">403.5</span></span></div><div class="cBG"><span style="font-size: small;">CAS—<i>132–17–2</i></span></div><span style="font-size: small;">A white, slightly hygroscopic, crystalline powder. M.p. 141° to 145°.</span><br />
<span style="font-size: small;">Soluble 1 in 0.7 of water, 1 in 1.5 of ethanol, and 1 in 2 of chloroform; practically insoluble in ether. </span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0020" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Dissociation Constant.</span></h2><div class="cAW"><span style="font-size: small;">Benzatropine pK<sub>a</sub>10.0 (20°).</span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0025" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Partition Coefficient.</span></h2><div class="cAW"><span style="font-size: small;">Benzatropine Log <i>P</i>(heptane), 0.4.</span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0030" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Colour Tests.</span></h2><div class="cAW"><span style="font-size: small;">Mandelin's Test—yellow; Marquis Test—yellow. </span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0035" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Thin–layer Chromatography.</span></h2><div class="cAW"><span style="font-size: small;">System TA—Rf 13; system TB—Rf 26; system TC—Rf 06; system TL—Rf 02; system TAE—Rf 06. (Acidified iodoplatinate solution, positive.) </span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0040" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Gas Chromatography.</span></h2><div class="cAW"><span style="font-size: small;">System GA—RI 2302; system GB—RI 2423. </span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0045" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine High Performance Liquid Chromatography.</span></h2><div class="cAW"><span style="font-size: small;">System HA—k 3.7 (tailing peak). </span></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0050" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Ultraviolet Spectrum.</span></h2><div class="cAW"><span style="font-size: small;">Aqueous acid—253, 259 nm (A<sup>1</sup><sub>1</sub>=14.5a). </span></div><div class="cAN" id="CLK0192U001"><span style="font-size: small;"></span> </div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0055" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Infra–red Spectrum.</span></h2><div class="cAW"><span style="font-size: small;">Principal peaks at wavenumbers 1054, 700, 742, 1191, 1204, 1075 cm<sup>−1</sup> (KBr disk). </span></div><div class="cAN" id="CLK0192I001"><span style="font-size: small;"></span> </div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0060" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Mass Spectrum.</span></h2><div class="cAW"><span style="font-size: small;">Principal ions at <i>m/z</i> 83, 140, 82, 124, 96, 97, 42, 125. </span></div><div class="cAN" id="CLK0192M001"><span style="font-size: small;"></span> </div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0065" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Quantification</span></h2><div class="cAQ" id="CLK0192P0075"><h4 class="cAW"><span style="font-size: small;">High performance liquid chromatography.</span></h4><div class="cAW"><span style="font-size: small;">In plasma—K. Selinger <i>et al</i>.,<i>J. Chromatogr.</i>,1989, <b>491</b>11, 248–252.</span></div></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0080" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Disposition in the Body.</span></h2><div class="cAW"><span style="font-size: small;">Absorbed after oral administration.</span></div><div class="cAP" id="CLK0192P0085"><div class="cAQ" id="CLK0192P0090"><h4 class="cAW"><span style="font-size: small;">Benzatropine Toxicity</span></h4><span style="font-size: small;">In a fatality attributed to the ingestion of an unknown quantity of benzatropine tablets, the following postmortem concentrations were reported: blood 0.7 mg/L, liver 1.6 μg/g, urine 0.8 mg/L. In a second case a liver concentration of 2.3 μg/g was found. [G. del Villar and M. Liddy,<i>Bull. Int. Assoc. Forensic Toxicol.</i>,1976, <b>12</b>2, 11–12.]</span><br />
<span style="font-size: small;">A 41–year–old male with a history of schizophrenia and drug abuse was found dead. Benzatropine was found at a concentration of 0.183 mg/L in his blood and 7.12 mg/L in his urine. [T. G. Rosano <i>et al</i>.,<i>J. Anal. Toxicol.</i>,1994, <b>18</b>6, 348–353.]</span></div></div></div><div style="text-align: justify;"></div><div class="cAO" id="CLK0192P0095" style="text-align: justify;"><h2 class="cAW"><span style="font-size: small;">Benzatropine Dose.</span></h2><div class="cAW"><span style="font-size: small;">0.5 to 6 mg of benzatropine mesilate daily.</span><br />
<div class="cAW"><div class="cAW"><span style="font-size: small;"><u><b>Reference </b></u></span></div><div class="cAW"><span style="font-size: small;">Clarke's Analysis of Drugs and Poisons</span></div></div></div></div></div></div>Sanalhttp://www.blogger.com/profile/14596236695526151439noreply@blogger.com0tag:blogger.com,1999:blog-3483751417218006682.post-52802594111250835052012-01-07T08:23:00.000-08:002012-11-01T20:13:01.649-07:00Laboratory Synthesis Of Diclofenac<div dir="ltr" style="text-align: left;" trbidi="on">
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<u><b>Chemical Synthesis Of Diclofenac</b></u></div>
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<br />
<span style="background-color: orange;">LINK TO THE PATENT DESCRIBING SYNTHESIS OF DICLOFENAC</span> <a href="http://www.google.com/patents?id=NVcaAAAAEBAJ&printsec=abstract&zoom=4&dq=3,558,690#v=onepage&q=3%2C558%2C690&f=false" target="_blank">CLICK HERE</a><br />
RN: 15307-86-5 EINECS: 239-348-5</div>
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<u><b>Diclofenac </b></u>MW: 296.15</div>
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<u><b>Diclofenac </b></u>MF: C14H11Cl2NO2</div>
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<u><b>Diclofenac </b></u>LD50: 170 mg/kg (M, p.o.);62.5 mg/kg (R, p.o.)</div>
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CN: 2- [(2 ,6- di chloro phenyl )amino ]benzene acetic acid</div>
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<b><u>monosodium salt</u></b></div>
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RN: 15307-79-6 EINECS: 239-346-4</div>
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<u><b>Diclofenac </b></u>MW: 318.14</div>
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<u><b>Diclofenac </b></u>MF: C14H10Cl2NNaO2</div>
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<u><b>Diclofenac </b></u>LD50: 116 mg/kg (M, i.v.); 390 mg/kg (M, p.o.);117 mg/kg (R, i.v.); 150 mg/kg (R, p.o.);</div>
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<u><b>Reference(s): </b></u></div>
<div style="text-align: justify;">
US 3 558 690 (Geigy; 26.1.1971; CH-prior. 8.4.1965, 25.2.1966, 30.3.1966, 20.12.1967).<br />
DAS 1 543 639 (Ciba-Geigy; appl. 7.4.1966; CH-prior. 8.4.1965).<br />
DAS 1 793 592 (Ciba-Geigy; appl. 7.4.1966; CH-prior. 8.4.1965).<br />
US 3 652 762 (Ciba-Geigy; 28.3.1972; prior. 9.12.1968, 29.9.1969, 14.4.1970).<br />
US 3 778 470 (Geigy; 11.12.1973; appl. 2.10.1970; prior. 4.4.1966).<br />
CH 492 679 (Geigy; appl. 30.3.1966).<br />
alternative synthesis:<br />
DOS 2 613 838 (Ikeda Mohando; appl. 31.3.1976; J-prior. 31.3.1975).</div>
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<br /></div>
<div class="cAO" style="text-align: justify;">
<div class="cAP" id="CLK0520P0001">
melting point diclofenac 156° to 158°.</div>
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<div class="cAO" id="CLK0520P0005" style="text-align: justify;">
<h2 class="cAW">
Diclofenac Sodium</h2>
<div class="cAP" id="CLK0520P0010">
<div class="cBG">
<i>Synonyms.</i> Diclofenacum Natricum; GP-45840.</div>
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<div class="cAP" id="CLK0520P0015">
<div class="cBG">
<i>Proprietary names.</i> Acoflam; Arthrotec; Cataflam; Dicloflex; Diclomax; Diclotard; Diclovol; Diclozip; Econac; Flamatak; Flamrase; Flexotard; Isclofen; Lofensaid; Motifene; Pennsaid; Rheumatac; Rhumalgan; Slofenac; Solaraze; Volraman; Volsaid; Voltaren(e); Voltarol.</div>
<div class="cBG">
<span class="cBL">C<sub>14</sub>H<sub>10</sub>Cl<sub>2</sub>NNaO<sub>2</sub></span>=<span class="cBM">318.1</span></div>
<div class="cBG">
CAS—<i>15307–79–6</i></div>
Crystals. MELTING POINT of diclofenac . 283° to 285°.<br />
Solubility at 25° (mg/mL): deionised water (pH 5.2) >9; methanol >24; acetone 6; acetonitrile <1; cyclohexane <1. </div>
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<div class="cAO" id="CLK0520P0020" style="text-align: justify;">
<h2 class="cAW">
<span style="font-size: small;">Dissociation Constant.</span></h2>
<div class="cAW">
<span style="font-size: small;">pK<sub>a</sub>4.2.</span></div>
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<div class="cAO" id="CLK0520P0025" style="text-align: justify;">
<h2 class="cAW">
<span style="font-size: small;">Partition Coefficient.</span></h2>
<div class="cAW">
<span style="font-size: small;">Log <i>P</i>(octanol/water), 4.5.</span></div>
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<h2 class="cAW">
<span style="font-size: small;">Colour Tests.</span></h2>
<div class="cAW">
<span style="font-size: small;">Liebermann's Test—red–brown; Mandelin's Test—red–brown; Marquis Test—brown (slow). </span></div>
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<h2 class="cAW">
<span style="font-size: small;">Thin–layer Chromatography.</span></h2>
<div class="cAW">
<span style="font-size: small;">System TA—Rf 90; system TD—Rf 25; system TE—Rf 12; system TF—Rf 27; system TG—Rf 29; system TAD—Rf 47; system TAE—Rf 90; system TAJ—Rf 40; system TAK—Rf 64; system TAL—Rf 84. (Chromic acid solution, red.) </span></div>
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<h2 class="cAW">
<span style="font-size: small;">Gas Chromatography.</span></h2>
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<span style="font-size: small;">System GA—diclofenac RI 2271, diclofenac-Me RI 2195, diclofenac-Me<sub>2</sub> RI 2220, M (OH-)-Me<sub>2</sub> RI 2460; system GB—RI 2231; system GD—diclofenac-Me RRT 1.42 (relative to n-C<sub>16</sub>H<sub>34</sub>); system GL—diclofenac-Me RI 2200, M (OH-)-Me<sub>2</sub> RI 2460. </span></div>
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<h2 class="cAW">
<span style="font-size: small;">High Performance Liquid Chromatography.</span></h2>
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<span style="font-size: small;">System HD—k 11.5; system HV—RRT 0.85 (relative to meclofenamic acid); system HX—RI 616; system HY—RI 592; system HZ—retention time 14.8 min; system HAA—retention time 22.1 min; system HAX—retention time 8.7 min; system HAY—retention time 10.0 min. </span></div>
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<h2 class="cAW">
<span style="font-size: small;">Ultraviolet Spectrum.</span></h2>
<div class="cAW">
<span style="font-size: small;">Aqueous acid—273 nm (A<sup>1</sup><sub>1</sub>=309b); aqueous alkali—275 nm (A<sup>1</sup><sub>1</sub>=351b). </span></div>
<div class="cAO" id="CLK0520P0065">
<h2 class="cAW">
<span style="font-size: small;">Quantification</span></h2>
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<h4 class="cAW">
<span style="font-size: small;">Gas chromatography.</span></h4>
<div class="cAW">
<span style="font-size: small;">In plasma: limit of detection 100 μg/L, ECD—M. Ikeda <i>et al</i>.,<i>J. Chromatogr.</i>,1980, <b>183(9) B Biomed. Appl.</b>, 41–47. In urine: diclofenac and hydroxy metabolites, ECD—W. Schneider and P. H. Degen,<i>J. Chromatogr.</i>,1981, <b>217</b>, 263–271.</span></div>
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<h4 class="cAW">
<span style="font-size: small;">Gas chromatography–mass spectrometry.</span></h4>
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<span style="font-size: small;">In plasma: limit of detection 2 μg/L, SIM—M. Del Puppo <i>et al</i>.,<i>Biol. Mass Spectrom.</i>,1991, <b>20</b>, 426–430. In plasma or urine: limit of detection 100 ng/L—A. Sioufi <i>et al</i>.,<i>J. Chromatogr.</i>,1991, <b>571</b>, 87–100. In plasma: limit of detection 0.2 μg/L—M. R. Borenstein <i>et al</i>.,<i>J. Chromatogr.</i>,1996, <b>685 B Biomed. Appl.</b>, 59–66. In urine: diclofenac and other NSAIDs—B. M. el Haj <i>et al</i>.,<i>Forensic Sci. Int.</i>,1999, <b>105</b>, 141–153. In urine: diclofenac and other NSAIDs, limits of detection 10 to 50 μg/L—H. H. Maurer <i>et al</i>.,<i>J. Anal. Toxicol.</i>,2001, <b>25</b>, 237–244.</span></div>
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<h4 class="cAW">
<span style="font-size: small;">High performance liquid chromatography.</span></h4>
<div class="cAW">
<span style="font-size: small;">In plasma: limit of detection 5 μg/L, UV detection—K. K. H. Chan <i>et al</i>.,<i>Anal. Lett. (Part B)</i>,1982, <b>15</b>, 1649–1663. In plasma: limit of detection 6 μg/L, fluorescence detection—B. Wiese and J. Hermansson,<i>J. Chromatogr.</i>,1991, <b>567</b>, 175–183. In plasma: limit of quantification 5 μg/L, UV detection—L. A. Brunner and R. C. Luders,<i>J. Chromatogr. Sci.</i>,1991, <b>29</b>, 287–291. In plasma or cerebrospinal fluid: limit of detection <1 μg/L, electrochemical detection—L. Zecca <i>et al</i>.,<i>J. Chromatogr.</i>,1991, <b>567</b>, 425–432. In plasma: limit of detection 1 μg/L, UV detection—S. R. Santos <i>et al</i>.,<i>Braz. J. Med. Biol. Res.</i>,1992, <b>25</b>, 125–128. In serum: limit of quantification 20 μg/L, fluorescence detection—J. Moncrieff,<i>J. Chromatogr.</i>,1992, <b>577</b>, 185–189. In plasma or synovial fluid: diclofenac and other NSAIDs—I. S. Blagbrough <i>et al</i>.,<i>J. Chromatogr.</i>,1992, <b>578</b>, 251–257. In plasma: limit of detection <2.5 μg/L, UV detection—R. B. Miller,<i>J. Chromatogr.</i>,1993, <b>616</b>, 283–290. In plasma or urine: limit of detection 0.2 mg/L, UV detection—A. Avgerinos <i>et al</i>.,<i>J. Chromatogr.</i>,1993, <b>619</b>, 324–329. In serum: limit of detection 10 μg/L—S. Y. Zhang et al.,<i>Yao Xue Xue Bao</i>,1994, <b>29</b>, 228–231. In aqueous humour: diclofenac and flurbiprofen, limit of detection for diclofenac 0.3 ng, UV detection—M. Riegel and P. P. Ellis,<i>J. Chromatogr.</i>,1994, <b>654 B Biomed. Appl.</b>, 140–145. In plasma: limit of detection 3 μg/L, UV detection—A. Hanses <i>et al</i>.,<i>Arch. Pharm. (Weinheim)</i>,1995, <b>328</b>, 257–260. In urine: diclofenac and its metabolites, limit of quantification 0.4 mg/L—R. J. Sawchuk <i>et al</i>.,<i>Pharm. Res.</i>,1995, <b>12</b>, 756–762. In urine: diclofenac and other NSAIDs, limit of detection for diclofenac 0.05 mg/L, UV detection—T. Hirai <i>et al</i>.,<i>J. Chromatogr. B Biomed. Sci. Appl.</i>,1997, <b>692</b>, 375–388. In serum or aqueous humour: limit of detection 1 μg/L, UV detection—O. Kuhlmann and G. J. Krauss,<i>J. Pharm. Biomed. Anal.</i>,1997, <b>16</b>, 553–559. In plasma: diclofenac and flurbiprofen—G. Giagoudakis and S. L. Markantonis,<i>J. Pharm. Biomed. Anal.</i>,1998, <b>17</b>, 897–901. In aqueous humour: diclofenac and oxybuprocaine, limit of detection for diclofenac 500 ng/L, electrochemical detection—O. Kuhlmann <i>et al</i>.,<i>J. Pharm. Biomed. Anal.</i>,1998, <b>17</b>, 1351–1356. In urine: diclofenac and other NSAIDs, limit of quantification for diclofenac 0.02 mg/L, UV detection—A. Bakkali <i>et al</i>.,<i>J. Chromatogr. B Biomed. Sci. Appl.</i>,1999, <b>729</b>, 139–145. In plasma: diclofenac and aceclofenac, limit of detection 10 μg/L—H. S. Lee <i>et al</i>.,<i>J. Pharm. Biomed. Anal.</i>,2000, <b>23</b>, 775–781. In plasma: limit of detection 5 μg/L—C. Arcelloni <i>et al</i>.,<i>J. Chromatogr. B Biomed. Sci. Appl.</i>,2001, <b>763</b>, 195–200.</span></div>
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<h2 class="cAW">
<span style="font-size: small;">Disposition in the Body.</span></h2>
<div class="cAW">
<span style="font-size: small;">Well absorbed after oral administration but undergoes significant first–pass metabolism. Up to about 70% of a dose is excreted in the urine in 3 days, including 20 to 40% as glucuronide and sulfate conjugates of the major metabolite 4′-hydroxydiclofenac (active) and up to about 15% as conjugates of unchanged diclofenac. Other metabolites identified in the urine include 5–hydroxydiclofenac (about 12% of the dose), 3′-hydroxydiclofenac, and 4′,5–dihydroxydiclofenac. About 10 to 20% of a dose is excreted in the bile as 4′-hydroxydiclofenac and less than 5% as unchanged drug. Diclofenac enters the synovial fluid and maximum concentrations are measured 2 to 4 h after the peak plasma levels have been reached. Diclofenac is excreted in breast milk but in quantities so small that no adverse effects on breast–fed infants would be expected.</span></div>
<div class="cAP" id="CLK0520P0095">
<div class="cAQ" id="CLK0520P0100">
<h4 class="cAW">
<span style="font-size: small;">Therapeutic concentration</span></h4>
<span style="font-size: small;">Following oral administration of 50 mg of diclofenac sodium three times a day to 4 subjects, peak plasma concentrations of 0.1 to 2.2 mg/L (mean 0.8) of diclofenac and 0.3 to 2.0 mg/L (mean 1.2) of 4′-hydroxydiclofenac were reported 3 h after a dose; peak concentrations in synovial fluid of 0.1 to 0.6 mg/L (mean 0.3) of diclofenac and 0.2 to 1.0 mg/L (mean 0.6) of 4′-hydroxydiclofenac were attained in 3 h; concentrations in synovial fluid exceeded those in plasma after 4 h. [P. D. Fowler <i>et al</i>.,<i>Eur. J. Clin. Pharmacol.</i>,1983, <b>25</b>, 389–394.]</span><br />
<span style="font-size: small;">Diclofenac was administered as a single oral 150 mg dose to healthy subjects (<i>n </i>= 6) and to patients with either chronic active hepatitis (<i>n</i> = 6) or alcoholic cirrhosis (<i>n</i>=6). Peak plasma concentrations of diclofenac, 3′-hydroxydiclofenac, 4′-hydroxydiclofenac, and 3′-hydroxy–4′,5–methoxydiclofenac of 5.699, 0.412, 2.613, and 0.385 mg/L were attained at 0.63, 0.79, 0.88, and 5.8 h, respectively, in healthy subjects. The equivalent respective values in patients with hepatitis were: 6.574, 0.392, 2.786, and 0.306 mg/L at 0.42, 0.58, 0.50, and 4.0 h and in patients with cirrhosis were: 11.59, 0.264, 2.481, and 0.191 mg/L at 0.33, 1.04, 0.75, and 7.0 h. [J. S. Lill <i>et al</i>.,<i>J. Clin. Pharmacol.</i>,2000, <b>40</b>, 250–257.]</span><br />
<span style="font-size: small;">In 20 healthy subjects given a single oral dose of diclofenac 100 mg as 2 different sustained–release tablets, respective peak plasma concentrations of 1.161 and 0.799 mg/L were attained in 4.2 and 4.5 h. [S. Zmeili <i>et al</i>.,<i>Int. J. Clin. Pharmacol. Ther.</i>,1996, <b>34</b>, 564–570.]</span></div>
<div class="cAQ" id="CLK0520P0105">
<h4 class="cAW">
<span style="font-size: small;">Toxicity</span></h4>
<span style="font-size: small;">A 19–year–old man was admitted to hospital following the ingestion of 1.5 g of diclofenac sodium and 4 g of chlormezanone. Plasma diclofenac concentrations of 60.1 mg/L and 0.19 mg/L were reported at 7 and 15 h, respectively; chlormezanone could not be determined. The subject recovered after about 2 days. [P. Netter <i>et al</i>.,<i>Eur. J. Clin. Pharmacol.</i>,1984, <b>26</b>, 535–536.]</span></div>
<div class="cAQ" id="CLK0520P0110">
<h4 class="cAW">
<span style="font-size: small;">Bioavailability.</span></h4>
<div class="cAW">
<span style="font-size: small;">About 50 to 60%</span></div>
</div>
<div class="cAQ" id="CLK0520P0115">
<h4 class="cAW">
<span style="font-size: small;">Half–life.</span></h4>
<div class="cAW">
<span style="font-size: small;">Plasma half–life, about 1 to 2 h; synovial fluid half–life 3 to 6 h.</span></div>
</div>
<div class="cAQ" id="CLK0520P0120">
<h4 class="cAW">
<span style="font-size: small;">Volume of distribution.</span></h4>
<div class="cAW">
<span style="font-size: small;">0.17 L/kg.</span></div>
</div>
<div class="cAQ" id="CLK0520P0125">
<h4 class="cAW">
<span style="font-size: small;">Clearance.</span></h4>
<div class="cAW">
<span style="font-size: small;">Plasma clearance, about 4 mL/min/kg.</span></div>
</div>
<div class="cAQ" id="CLK0520P0130">
<h4 class="cAW">
<span style="font-size: small;">Protein binding.</span></h4>
<div class="cAW">
<span style="font-size: small;">In plasma, more than 99%.</span></div>
</div>
<div class="cAQ" id="CLK0520P0135">
<h4 class="cAW">
<span style="font-size: small;">Note.</span></h4>
<div class="cAW">
<span style="font-size: small;">For reviews of diclofenac see R. W. Brogden <i>et al</i>.,<i>Drugs</i>,1980, <b>20</b>, 24–48 and N. M. Davies and K. E. Anderson,<i>Clin. Pharmacokinet.</i>,1997, <b>33</b>, 184–213.</span></div>
</div>
</div>
</div>
<div class="cAO" id="CLK0520P0140">
<h2 class="cAW">
<span style="font-size: small;">Dose.</span></h2>
<div class="cAW">
<span style="font-size: small;">75 to 150 mg of diclofenac sodium daily in divided doses.</span></div>
</div>
<div class="cAW">
<div class="cAW">
<span style="font-size: small;"><u><b>Reference </b></u></span></div>
<div class="cAW">
<span style="font-size: small;">Clarke's Analysis of Drugs and Poisons</span><br />
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