Patent CA-1150246-A (CA)
Inventor: EDER ULRICH
IPC: C07H13/10
Filed: 1980-08-28
Granted: 1983-07-19
Abstract: ABSTRACT OF THE DISCLOSURE          The invention provides a method of preparing .beta.-carbolin-3-carboxylic acid derivatives of the general formula I                                  (I) wherein X is an oxygen or sulphur atom, NR10, wherein R10 is a hydrogen atom, a lower alkyl or cycloalkyl group;          R3  is an alkoxy, aryloxy or aralkoxy group optionally substi-tuted with one or more hydroxy groups; or NR11R12, wherein R11 and R12 are similar or different and each represents a hydrogen atom, a hydroxy, an alkyl, aryl, aralkyl or cycloalkyl group optionally substituted with a hydroxy, carboxamide, an alkoxycarbonyl, a monosaccharide or a heterocyclic group; or an amino group optionally substituted with an alkyl, aryl, aralkyl or cycloalkyl group; or wherein R11 and R12 together with the adjacent nitrogen atom form a 5-, 6- or 7-membered heterocyclic ring; with the proviso that R11 and R12 cannot both be a hydroxy group; or wherein X and R represent a nitrogen atom;          R4  is a hydrogen atom, an alkyl group, a cycloalkyl group, an aralkyl group, a phenyl or an alkoxypnenyl group contain-ing up to 10 carbon atoms, RA  is F, Cl, Br, J, NO2, NR13R14, NHCOR13, CN, COO R13 or OR13 wherein R13 and R14 each is a hydrogen atoms or an alkyl group containing up to 6 carbon atoms and option-ally substituted with a hydroxy group or a halogen atom; SCH3 or SO2NR11R12, wherein R11 and R12 have the meaning as given above and wherein each molecule may contain two or more identical or different RAs: R9  is a hydrogen atom, an alkyl, group containing up to 8 carbon atoms or an alkoxy carbonyl group. with the provisos:-that R11 and R12 cannot both represent a hydrogen atom, when X represents an oxygen atom and when R4, RA and R9 each represents a hydrogen atom, that one of the substituents R11 and R12 cannot represent a hydrogen alom when the other substituent represents an amino group and when X represents an oxygen atom and R4, RA and  R9  each represents a hydrogen atom, and that R4, RA and R9 each cannot represent a hydrogen atom when X represents an oxygen atom and R3 reprcscnts OCH3, comprising (a)  dehydrogenating a compound of the general formula II                                                 (II) wherein X, R3, R4, RA and R9 have the meanings given above, (b)  esterifying a compound of the general formula III                                         (III) wherein X, R4  RA and R9 have the meanings given above, and amidating, if desired or reesterifying if desired, the ester thus obtained, (c) reacting a compound of the general formula III, wherein X          R4, RA and R9 have the meanings given above or a functional derivative of said compound, with a compound of the general formula IV       wherein R11 and R12 have the meanings given above and reacting, if desired the amide thus formed with P2S5 to form the corres-ponding thioamide or in case R11 is a hydrogen atom, with thionyl chloride to form a compound of the general formula V                                         (V) and reacting the compound thus formed with a compound of the general formula H2NR10, wherein R10 has the meaning given above, to form a compound of the general formula VI                                (VI) (d)  reacting a nitrile of the general formula VII                              (VII) wherein R4, RA and R9 have the meanings given above with an alcohol and anhydrous hydrogen chloride to form the corresponding imino compound and then reacting said imino compound with a compound of the general formula IV, wherein R11 and R12 have the meanings given above to form the corresponding amidine, (e)  halogenating a compound of the general formula 1, wherein X, R3, R4, RA and R9 have the meanings given above, and alkoxyl-ating, if desired or thioalkylating, if desired, the halogenated compound thus formed, or (f)      nitrating a compound of the general formula 1, wherein X, R3, R4, RA and R9 have the meanings given above, and reducing, if desired, the nitrated compound thus formed to form the corresponding amino compound, converting, if de-sired, the amino compound into the corresponding nitrile or halogenated compound, hydrolyzing, if desired, the nitrile to form the corresponding acid, or acylating, if desired, the amino compound to form the corresponding amide.