Patent ID: 6335448
Filing Date: 2002-01-01
Classification: A61P,C07D

Abstract:
A method for preparing a compound of formula (I): or a pharmaceutically acceptable salt form thereof, wherein:Ar is an optionally substituted phenyl group, or a naphthyl or C5-7 cycloalkdienyl group, or an optionally substituted single or fused ring heterocyclic group, having aromatic character, containing from 5 to 12 ring atoms and comprising up to four hetero-atoms in the or each ring selected from S, O, N; R is linear or branched C1-8 alkyl, C3-7 cycloalkyl, C4-7 cycloalkylalkyl, an optionally substituted phenyl group or a phenyl C1-6 alkyl group, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatom selected from O and N, hydroxy C1-6 alkyl, di C1-6 alkylaminoalkyl, C1-6 acylaminoalkyl, C1-6 alkoxyalkyl, C1-6 alkylcarbonyl, carboxy, C1-6 alkoxycarbonyl, C1-6 alkoxycarbonyl C1-6 alkyl, aminocarbonyl, C1-6 alkylaminocarbonyl, di C1-6 alkylaminocarbonyl; or is a group â€”(CH2)pâ€” when cyclized onto Ar, where p is 2 or 3; R1 and R2, which may be the same or different, are independently hydrogen or C1-6 linear or branched alkyl, or together form a â€”(CH2)nâ€” group in which n represents 3, 4, or 5; or R1 together with R forms a group â€”(CH2)qâ€”, in which q is 2, 3,4 or 5; R3 and R4, which may be the same or different, are independently hydrogen, C1-6 linear or branched alkyl, C1-6 alkenyl, aryl, C1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, trifluoromethyl, amino, mono- and di-C1-6 alkylamino, â€”O(CH2)râ€”NT2, in which r is 2, 3, or 4 and T is C1-6 alkyl or it forms a heterocyclic group in which V and V1 are hydrogen and u is 0, 1 or 2; â€”O(CH2)sâ€”OW2 in which s is 2, 3, or 4 and W is C1-6 alkyl; hydroxyalkyl, mono- or di-alkylaminoalkyl, acylamino, alkylsulphonylamino, aminoacylamino, mono- or di-alkylaminoacylamino; with up to four R3 substituents being present in the quinoline nucleus; or R4 is a group â€”(CH2)tâ€” when cyclized onto R5 as aryl, in which t is 1, 2, or 3; and R5 is branched or linear C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkylalkyl, optionally substituted aryl, wherein the optional substituent is one of hydroxy, halogen, C1-6 alkoxy or C1-6 alkyl, or an optionally substituted single or fused ring heterocyclic group, having aromatic character, containing from 5 to 12 ring atoms and comprising up to four hetero-atoms in the or each ring selected from S, O, N; comprising: 1) adding a compound of formula (III): to base in a suitable solvent, to form a first reaction mixture, adding to the first reaction mixture a compound of formula (II): to form a second reaction mixture, and heating the second reaction mixture to form a compound of formula (IV): 2) isolating the compound of formula (IV) and then reacting the compound of formula (IV), in a suitable solvent, with a base to form a third reaction mixture, cooling the third reaction mixture, and adding thionyl chloride to form a fourth reaction mixture; 3) adding a compound of formula (V): to the fourth reaction mixture to form a fifth reaction mixture;4) heating the fifth reaction mixture; and 5) optionally converting the compound of formula (I) to a pharmaceutically acceptable salt thereof, wherein Ar, R, R1, R2, R3, R4, and R5 as used in a compound of formulae (II) through (V) are as defined for a compound of formula (I).