| 摘要 |
The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, —where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, R1 and R2 independently represent hydrogen atom or a straight or branched C1-10 alkyl- or aralkyl-group, optionally substituted with —ONO2 group, or an aralkyl- or aryl-group, which contains heteroatom, R3 represents a straight or branched, saturated or unsaturated C4-6 hydrocarbon group, or a C4-10 alkylcycloalkyl- or cycloalkyl-group, or an optionally with alkyl group or halogen atom substituted phenyl-, C7-10 alkylaryl- or hetaryl-group, Y represents (CH2)n group or 0 atom or S atom, and where n=0-3.; |
| 主权项 |
1. Process for the preparation of prostaglandin amides of the general formula (I), where in the formulathe bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation,Q represents hydroxyl-group and Z represents hydroxyl-group,R1 and R2 independently represent (i) a hydrogen atom, (ii) a straight or branched C1-10 alkyl- or aralkyl-group, optionally substituted with —ONO2 group, or (iii) an aralkyl- or aryl-group, which contains heteroatom,R3 represents a phenyl group optionally substituted with an alkyl group or a halogen atom,Y represents (CH2)n group or O atom, and where n is 1, 2, or 3,characterized in that an acid of the general formula (II),where in the formulathe bonds marked with dotted lines may be single or double bonds, in the case of double bonds at positions 5,6 and 13,14 they may be in cis or in trans orientation,Q represents hydroxyl-group and Z represents hydroxyl-group,R3 represents a phenyl group optionally substituted with an alkyl group or a halogen atom,Y represents (CH2)n group or O atom, and where n is 1, 2, or 3,is reacted
i.) with a compound suitable to introduce group R4, where R4 representsthe group of formula a.)and reacting the amide of the general formula (III), thus obtainedwhere the meanings of Q, Z, R3, R4, Y and n are as defined above, with an amine of the general formula (IV)
NHR1R2 IV where R1 and R2 have the meanings as defined above, or ii.) with a compound suitable to introduce group R5, where R5 representsa group of formula b.), c.), d.) or e.), where (X) stands for halogen or hydrogen atom—and reacting the activated ester of the general formula (V), thus obtainedwhere the meanings of Q, Z, R3, R5, Y and n are as defined above, with an amine of the general formula (IV), where the meanings of R1 and R2 are as defined above, or
iii.) with an amine of the general formula (IV), —where the meanings of R1 and R2 are as defined above—in the presence of 2-chloro-1,3-dimethylimidazolinium chloride and a base. |
