Famotidine Synthesis
Use: ulcer therapeutic, H2-receptor antagonist
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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.
SYNTHESIS
REFERENCE
Drugs Fut 1983, 8, 1, 14
US 4283408
DOS 2 951 675 (Yamanouchi; appl.
21.12.1979; J-prior. 2.8.1979).
DOS 3 008 056 (Yamanouchi; appl.
3.3.1980; J-prior. 6.3.1979, 23.6.1979).
GB 2 052 478 (Yamanouchi; appl.
6.3.1980; J-prior. 6.3.1979, 23.6.1979).
GB 2 055 800 (Yamanouchi; appl.
20.12.1979; J-prior. 2.8.1979).
synthesis of S-[2-aminothiazol-4-ylmethyl]isothiourea:
Spragne, J.M.; Lund, A.H.; Ziegler,
C.: J. Am. Chem. Soc. (JACSAT) 68, 2155 (1946).
