1,1-Dichloroacetone → HCID 178479418, compound

HRID 341972

Reaction equation

HRID 341972 reaction equation
C1[S:5][C:4]([NH:6][C:7]([NH2:9])=[NH:8])=[N:3]C=1CSCCC(NS(N)(=O)=O)=N.NCCC1N=CNC=1.[H][H].C(CCSCC1N=C(NC(N)=N)SC=1)#N.NN=CNC(N)=S.[Cl:53][CH:54](Cl)[C:55](=[O:57])[CH3:56]>CC(C)=O>[ClH:53].[Cl:53][CH2:54][C:55]1([OH:57])[CH2:56][S:5][C:4]([NH:6][C:7]([NH2:9])=[NH:8])=[N:3]1

Participants

7

Reactant 5

HCID 105671,1-DichloroacetoneHCID 178418935HCID 178418935, compoundHCID 178510869HCID 178510869, compoundHCID 178511217HCID 178511217, compoundHCID 178514401HCID 178514401, compound

Product 1

HCID 178479418HCID 178479418, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Famotidine is a well-known histamine H2-receptor antagonist and gastric acid secretion inhibitor. A key intermediate for the preparation of this compound is N-[4-(cyanoethylthiomethyl)-2-thiazolyl]guanidine (also known as N-[4-[[(2-cyanoethyl)-thio]methyl]-2-thiazoyl]guanidine). To prepare this intermediate U.S. Pat. Nos. 4,562,261 and 4,609,737 describe a route based on N-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride as the starting material. The synthesis involves preparing this starting material by portionwise addition of (aminoiminomethyl)thiourea to dichloroacetone in acetone at temperatures of about -5° to -7° C. and stirring the resultant mixture for 5 days at below 0° C. The resultant N-[4-(chloromethyl)-4,5-dihydro-4-hydroxy-2-thiazolyl]-guanidine hydrochloride is isolated, purified and converted to N-[4-[[(2-aminoiminomethyl)thio]methyl]-2-thiazoyl]guanidine) dihydrochloride by reaction with thiourea. Without isolating this intermediate, the reaction mixture is cooled below 10° C. and to the solution are added 3-chloropropionitrile and isopropyl alcohol, followed by dropwise addition of aqueous NaOH whereby crystals of N-[4-(cyanoethylthiomethyl)-2-thiazolyl]guanidine are formed.

Workup

  1. customA key intermediate for the preparation of this compound
  2. customTo prepare this intermediate U.S
  3. custompreparing this starting material

Sources & evidence

ORD record
ord-d7ece887dd4a4aa0937e66bb132fb550
Source dataset
uspto-grants-1999_01
Patent number
US05856500

Linked notes

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