Reaction equation
N=O.[NH:3]([C:7]1[S:8][CH:9]=[C:10]([CH2:12][S:13][CH2:14][CH2:15][C:16]#[N:17])[N:11]=1)[C:4]([NH2:6])=[NH:5].[S:18]([NH2:22])([NH2:21])(=[O:20])=[O:19]>>[CH:9]1[S:8][C:7]([NH:3][C:4]([NH2:6])=[NH:5])=[N:11][C:10]=1[CH2:12][S:13][CH2:14][CH2:15][C:16]([NH:21][S:18]([NH2:22])(=[O:20])=[O:19])=[NH:17]Participants
Procedure
An inproved method is disclosed in the European Patent Application No. 128,736 of the same company, where the chromatographic purification could be avoided only by preparing and using an iminoether base of substantially higher purity. From 3-(2-guanidino-thiazol-4-yl-methylthio)-propionitrile solid iminoether base was prepared with a yield of 78.8%, which was reacted with 2.2 molar equivalents of sulfamide in a methanolic medium, at 20° to 30° C. for three days. The crude product obtained with a yield of 62% was recrystallized from aqueous dimethyl formamide, and the obtained material was again precipitated with a base, after dissolution in a mixture of water and acetic acid. The total yield for crude famotidine was accordingly merely 48.8%. The main disadvantage of this process is the high consumption of sulfamide, the many and cumbersome steps involved in the process and that it is very time consuming.
Workup
- custom128,736 of the same company, where the chromatographic purification
- customcould be avoided only by preparing
- customThe crude product obtained with a yield of 62%
- customwas recrystallized from aqueous dimethyl formamide
- customthe obtained material was again precipitated with a base
- dissolutionafter dissolution
- additionin a mixture of water and acetic acid
Sources & evidence
- ORD record
- ord-ce955d891851460985df8df6315254cf
- Source dataset
- uspto-grants-1989_05
- Patent number
- US04835281
Linked notes
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