| 摘要 |
A process for the preparation of compounds of Formula I and their pharmaceutically acceptable acid addition salt wherein, R1 is phenyl or substituted phenyl R2 is selected from a group consisting of phenyl which is unsubstituted or substituted with 1 or 2 substituents, each independently selected from Cl, F, or pyridine, or naphthalene, or NHCOR4 wherein R4 is aryl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heterocyclyl. R3 is selected from a group of formula wherein R5 is phenyl which is unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, nitro, amino, haloalkyl, haloalkoxy etc.; unsubstituted or substituted benzyl; unsubstituted or substituted heteroaryl; unsubstituted or substituted heteroaroyl; unsubstituted or substituted diphenylmethyl, <?in-line-formulae description="In-line Formulae" end="lead"?>n=0-2 and<?in-line-formulae description="In-line Formulae" end="tail"?> <?in-line-formulae description="In-line Formulae" end="lead"?>X--NCH3, CH2, S, SO, or SO2 <?in-line-formulae description="In-line Formulae" end="tail"?> Such that when R2 is phenyl, which is unsubstituted or substituted with 1 or 2 substituents, each independently selected from Cl, F; R5 is not C1-C4 alkyl, or X is not -NCH3, CH2, S, SO, or SO2, when n=1, or X is not -CH2 when n=0; comprising the steps of (a) reacting compound of Formula II with a chlorinating agent in the presence or absence of catalytic amount of N,N-dimethylformamide to yield the compound of Formula III, (b) reacting the compound of Formula III with a compound of Formula R1H (R1 is as defined above), in presence of a Lewis acid to obtain the compound of Formula IV, (c) reacting the compound of Formula IV with a compound of Formula R2NH2 (R2 is as defined above) in presence of catalytic amounts of an aryl or alkyl sulphonic acid in an organic solvent to obtain the compound of Formula V, (d) reacting the compound of Formula V with various secondary amines of the Formula R3H (R3 is as defined above) in the presence of formaldehyde and acetic acid in acetonitrile followed by crystallization yield the compound of Formula I, (e) purifying the compound of Formula I by crystallization, (f) converting the purified compound of Formula I to a pharmaceutically acceptable acid addition salt.
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