Patent GB-1213049-A (GB)
Title: Mercaptopropionic acids
Inventor: SHEN TSUNG-YING
IPC: C07C45/63
Filed: 1968-12-16
Abstract: 1,213,049. Mercaptopropionic acid derivatives. MERCK & CO. Inc. 16 Dec., 1968 [20 Dec., 1967], No. 59681/68. Heading C2C. [Also in Division A5] Novel, therapeutically active compounds I, II, III and IV (including optically active forms) wherein [Het] is a heteroaryl radical of not more than three fused rings each of six atoms or fewer that contains one or more similar or dissimilar atoms from among N, O and S as hetero atoms and that is optionally substituted by one or more alkyl, alkenyl, cycloalkyl, OH, alkoxy, aryl, aralkyl, SH, alkylthio, halo, CN, CO 2 H, NO 2 , NH 2 , alkylamino or dialkylamino, [Ar] is a benzenoid or non-benzenoid carbocyclic aromatic radical that contains not more than three fused rings each of six carbons or fewer and that is optionally substituted by one or more substituents as defined for [Het] and also including trihalomethyl, alkanoyl, aryloxy, aralkoxy, trifluoromethylthio, alkylsulphonyl and sulphamoyl, each of R α , R #  and R<SP>11</SP> is H, alkyl, cycloalkyl, aryl or aralkyl or two of R α  and R #  together form a cycloalkyl group with the carbon atom(s) that they are attached to, A is -COY, -CH 2 Y or COOM (Y is OH, NH 2 , alkyl-, dialkyl- or cycloalkyl-amino, N-heterocyclo, alkoxy or benzyloxy and M is a salt forming cation), provided that, in II, if [Ar] is unsubstituted phenyl and Y is OH, then at least one of R<SP>11</SP>, R a  and R #  is other than H, and that if Y is Et 2 N-, Ar is unsubstituted phenyl, and one R<SP>11</SP> is phenyl and the other is H then at least one of R α  and R #  is other than H, and provided that, in IV, if [Ar] is unsubstituted phenyl, 4-methoxyphenyl, 2- or 4- nitrophenyl, 2-aminophenyl or 4-chlorophenyl and Y is OH, then at least one of R<SP>11</SP>, R α  and R #  is other than H, that if one of R α  or R #  is Me, Et or Ph, [Ar] is unsubstituted phenyl and Yis OH, then at least one of R<SP>11</SP> and the other R α S and R # S is other than H, that if one of R<SP>11</SP> is Me, Ph or benzyl, [Ar] is unsubstituted phenyl and Y is OH at least one of R α , R #  and the other R<SP>11</SP> is other than H, and that if both R<SP>11</SP>S are Ph, [Ar] is Ph and Y is OH then at least one of R α  and R #  is other than H. are obtained: (a) by reacting a thiol, HS-C(R # ) 2 ÀC(Rα) 2 ÀCOY, with a halo compound, [Ar]- or [Het]-C(R<SP>11</SP>) 2 - halogen; or (b) by reacting a thiol, [Ar]- or [Het]-C(R<SP>11</SP>) 2 SH, with a halo compound, halogenÀC(R # ) 2  C(R α ) 2  COY. Standard methods may be used, where appropriate, for converting compounds of the invention into esters, ethers, amides, amines and alcohols of the invention; also, where appropriate, substituent groups can be converted one into the other. 4 - Hydroxymethylthiazole is prepared by treating 4 - formylthiazole with sodium borohydride in the presence of ethanol. 4 - Carboxyimidazole, obtained by hydrolysis of 4 - anilinocarbonylimidazole (prepared by the interaction of aniline and 4,5 - dicarboxyimidazole), is esterified to afford 4 - ethoxycarbonylimidazole which is converted to 4- hydroxymethylimidazole utilizing lithium aluminium hydride. 3 - (2 - Chlorobenzylthio) - and 3 - (2<SP>1</SP> - pyridylmethylthio) - propionyl chlorides are prepared from the corresponding acids utilizing thionyl chloride.