Patent ID: 6762301
Filing Date: 2004-07-13
Classification: C07D

Abstract:
A process for the preparation of a compound of the formula in racemic or enantiomeric form or any combinations of these forms,R1 is selected from the group consisting of lower alkyl, lower alkenyl, lower alkynyl, lower haloalkyl, lower alkoxy lower alkyl and lower alkylthio lower alkylthio lower alkyl R2, R3 and R4 are individually (i) II, halo, lower halo alkyl, lower alkyl, lower alkenyl, cyano, lower cyano alkyl, nitro, lower nitroalkyl, amido, lower amino alkyl, hydrazino, lower hydrazino alkyl, azido, lower azido alkyl, â€”(CH2)mNR6R7, â€”(CH2)mOR6, â€”(CH2)mSR6, â€”(CH2)mCO2NR6, â€”(CH2)mNR6C(O)R8, â€”(CH2)mC(O)R8, â€”(CH2)mOC(O)R8, â€”O(CH2)mNR6R7, â€”OC(O)NR6R7, OC(O) (CH2)mCO2R6, and (ii) â€”(CH2)n[N&boxH;X], â€”OC(O)[N&boxH;X], â€”(CH2)mOC(O)[Nâ€”X], aryl, aryl lower alkyl, each unsubstituted or substituted by a member selected from the group consisting of lower alkyl, halo, nitro, amino, lower alkylamino, lower haloalkyl, lower hydroxy alkyl, lower alkoxy and lower alkoxy lower alkyl, or R2 and R3 form together a chain with 3 or 4 members in which the elements of the chain are selected from the group consisting of CH, CH2, O, S, N or NR9; R5 is selected from the group consisting of I) H, halo, lower halo alkyl, lower alkyl, lower alkoxy, lower alkoxy lower alkyl, lower alkylthio lower alkyl, cycloalkyl, cycloalkyl lower alkyl, cyano, cyano alkyl, lower alkyl sulfonyl lower alkyl, lower hydroxy alkyl, nitro, â€”(CH2)mC(O)R8, â€”(CH2)mNR5R7, â€”(CH2)mN(CH3)(CH2)nNR6R7, â€”(CH2)mOC(O)R8, â€”(CH2)mOC(O)NR6R7, â€”(CH2)mS(O)qRH, â€”(CH2)mP(O)R12R13 and â€”(CH2)2P(S)R12R13, or ii) â€”(CH2)n[N&boxH;X], â€”OC(O)[N&boxH;X], â€”CH2)mOC(O)[N&boxH;X], aryl or aryl lower alkyl, each unsubstituted or substituted with a member selected from the group consisting of lower alkyl, halo, nitro, amino, lower alkyl amino, lower halo alkyl, lower hydroxy alkyl, lower alkoxy and lower alkoxy lower alkyl; R6 and R7 are independently selected from the group consisting of I) H, lower alkyl, lower hydroxy alkyl, lower alkyl amino alkyl, lower amino alkyl, cycloalkyl, lower cycloalkyl alkyl, lower alkenyl, lower alkoxy lower alkyl, and lower halo alkyl, or ii) aryl or aryl lower alkyl, each unsubstituted or substituted with a member selected from the group consisting of lower alkyl, halo, nitro, amino, lower alkyl amino, lower halo alkyl, lower hydroxy alkyl, lower alkoxy and lower alkoxy lower alkyl; R8 is selected from the group consisting of I) H, lower alkyl, lower hydroxy alkyl, amino, lower alkyl amino, lower alkyl amino lower alkyl, lower amino alkyl, cycloalkyl, lower cycloalkyl alkyl, lower alkenyl, lower alkoxy, lower alkoxy lower alkyl, and lower halo alkyl, or ii) aryl or aryl lower alkyl, each unsubstituted or substituted with a member selected from the group consisting of lower alkyl, halo, nitro, amino, lower alkyl amino, lower halo alkyl, lower hydroxy alkyl, lower alkoxy and lower alkoxy lower alkyl; R9 is selected from the group consisting of i) H, lower alkyl and lower halo alkyl, or ii) aryl substituted by at least one member of the group consisting of lower alkyl, halo, nitro, amino, lower alkyl amino, lower halo alkyl, lower hydroxy alkyl, lower alkoxy and lower alkoxy lower alkyl; R10 is selected from the group consisting of I) H, lower alkyl, lower halo alkyl, lower alkoxy and aryl or ii) aryl substituted by at least one member of the group consisting of lower alkyl, l ower halo alkyl, lower hydroxy alkyl and lower alkoxy lower alkyl; R11 is selected from the group consisting of lower alkyl, aryl, â€”(CH2)mOR14, â€”(CH2)mSR14, â€”(CH2)2NR14R15 and(CH2)m[N&boxH;X]; R12 and R13 are independently selected from the group consisting of lower alkyl, aryl, lower alkoxy, aryloxy and amino; R14 and R15 are independently selected from the group consisting of H, lower alkyl and aryl; R18 and R19 are independently selectd from the group consisting of H, halo, lower alkyl, lower alkoxy and hydroxy; R20 is H or halo; m is an integer between 0 and 6; n is 1 or 2; and q is an integer from 0 to 2; and [N&boxH;X] is a heterocyclic group with 4 ti 7 ring members with the nitrogen atom which is a member of the heterocyclic ring, and X is the chain necessary to complete said heterocyclic group and is selected from the group consisting of O, S, CH2, CH, N, NR9 and COR10; and a pharmaceutically acceptable salt of the latter; comprising reacting a compound of the formula wherein R1, R18 and R19 have the above meaning and R20 is hydrogen or halogen with a 2-halo-3-quinoline-methanol of the formula wherein R2, R3, R4 and R5 have the above meaning and X is halogen to produce a compound of the formula wherein R1, R2, R3, R4, R5, R18, R19 and R20 have the above meaning; cyclizing the compound of formula O to obtain the compound of formula I.