Patent CA-1263114-A (CA)
Inventor: CRENSHAW RONNIE RAY
IPC: C07D277/28
Filed: 1982-11-02
Granted: 1989-11-21
Abstract: ABSTRACT              Novel intermediates useful in the processes of making histamine H2-antagonists of the formula   wherein p is 1 or 2;            R7 is a leaving group selected from halogen, (lower)alkoxy, (lower)alkylthio, phenoxy, phenylthio, substituted phenoxy and substituted phenylthio wherein the phenyl ring may contain 1 or 2 substitutents selected from halogen, (lower)alkyl, (lower)alkoxy and nitro; and R12 is A(CH2)mZ(CH2)nNH-, R2R3N- or HS(CH2)nNH-;     in which R2 and R3 each are independently hydrogen, (lower)-alkyl, (lower)alkenyl, (lower)alkynyl, cyclo(lower)alkyl, cyclo(lower)alkyl(lower)alkyl, hydroxy(lower)alkyl, (lower)-alkoxy(lower)alkyl, (lower)alkylthio(lower)alkyl, amino-(lower)alkyl, (lower)alkylamino(lower)alkyl, di(lower)-alkylamino(lower)alkyl, pyrrolidino(lower)alkyl, piperidino-(lower)alkyl, morpholino(lower)alkyl, piperazino(lower)-alkyl, pyridyl(lower)alkyl, amino, (lower)alkylamino, di(lower)alkylamino, 2,2,2-trifluoroethyl, 2-fluoroethyl, hydroxy, (lower)alkoxy, 2,3-dihydroxypropyl, cyano, cyano(lower)alkyl, amidino, (lower)alkylamidino, A'-(CH2)m,Z'(CH2)n,-, phenyl, phenyl(lower)alkyl, substituted phenyl or substituted phenyl(lower)alkyl, wherein the phenyl ring may contain one or two substituents independently selected from (lower)alkyl, hydroxy, (lower)-alkoxy and halogen, or one substituent selected from methylenedioxy, trifluoromethyl and di(lower)alkylamino;     provided that R2 and R3 may not both be cyclo(lower)alkyl, phenyl, substituted phenyl, amino, (lower)alkylamino, di(lower)alkylamino, hydroxy, (lower)alkoxy, cyano, amidino, (lower)alkylamidino or A'-(CH2)m'  Z'(CH2)n'-; or R2 and R3, taken together, may be -CH2CH2X(CH2)r-; r is an integer of from 1 to 3, inclusive; X is methylene, sulfur, oxygen or N-R4, provided that, when p is 2 and R7 is methoxy, R2 and R3 taken together with the nitrogen to which they are attached, may not be morpholino or piperidino, and that, when r is 1, X is methylene;          R4 is hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, (lower)alkanoyl or benzoyl;           m and m' each are independently an integer of from zero to 2, inclusive;           n and n' each are independently an integer of from 2 to 4, inclusive;           Z and Z' each are independently sulfur, oxygen or methylene;           A and A' each are independently phenyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, furyl, thienyl or pyridyl; provided that A and A' independently may contain one or two substituents, the first substituent being selected from (lower)alkyl, hydroxy, trifluoromethyl, halogen, amino, hydroxymethyl, (lower)alkoxy,               and -(CH2)qNR5R6 and the second substituent being selected from (lower)-alkyl, hydroxy, trifluoromethyl, halogen, amino, hydroxymethyl and (lower)alkoxy;     q is an integer of from 0 to 6, inclusive; each R4 independently is as defined above, or the two R4 groups, taken together, may be ethylene; and R5 and R6 each are independently hydrogen, (lower)alkyl, (lower)alkenyl, (lower)alkynyl, cyclo(lower)-alkyl or phenyl, pxovided that R5 and R6 may not both be cyclo(lower)alkyl or phenyl; or R5 and R6, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, morpholino, piperidino, methylpiperidino, N-methylpiperazino or homopiperidino;        or a salt, hydrate, solvate or N-oxide thereof, and a process for preparing such compound.