Patent ID: 7223861

Claim:
A process for preparing compounds having the structural formula I or a pharmaceutically acceptable salt thereof, wherein R is R 1 -furanyl, R 1 -thienyl, R 1 -pyridyl, R 1 -pyridyl N-oxide, R 1 -oxazolyl, R 10 -phenyl, R 1 -pyrrolyl or cycloalkenyl; X is C 2 –C 6 alkylene; Y is —N(R 2 )CH 2 CH 2 N(R 3 )—, —OCH 2 CH 2 N(R 2 )—, —(CH 2 ) 2 —NH—, or and Z is R 5 -phenyl, R 5 -phenylalkyl, R 5 -heteroaryl, diphenylmethyl, R 6 —C(O)—, R 6 —SO 2 —, or phenyl-CH(OH)—; or when Q is Z is also phenylamino or pyridylamino; or Z and Y together are R 1 is 1 to 3 substituents independently selected from hydrogen, alkyl, —CF 3 , halogen, —NO 2 , —NR 12 R 13 , alkoxy, alkylthio, alkylsulfinyl, and alkylsulfonyl; R 2 and R 3 are independently selected from the group consisting of hydrogen and alkyl; m and n are independently 2–3; Q is R 4 is 1–2 substituents independently selected from the group consisting of hydrogen and alkyl, or two R 4 substituents on the same carbon can form ═O; R 5 is 1 to 5 substituents independently selected from the group consisting of hydrogen, halogen, alkyl, hydroxy, alkoxy, —CN, dialkyl-amino, —CF 3 , —OCF 3 , acetyl, —NO 2 , hydroxyalkoxy, alkoxyalkoxy, dialkoxy-alkoxy, alkoxy-alkoxy-alkoxy, carboxy-alkoxy, alkoxycarbonylalkoxy, cycloalkyl-alkoxy, dialkyl-amino-alkoxy, morpholinyl, alkyl-SO 2 —, alkyl-SO 2 -alkoxy, tetrahydropyranyloxy, alkylcarbonyl-alkoxy, alkoxycarbonyl, alkylcarbonyloxy-alkoxy, —SO 2 NH 2 , or phenoxy; or adjacent R 5 substituents together are —O—CH 2 —O—, —O—CH 2 CH 2 —O—, —O—CF 2 —O— or —O—CF 2 CF 2 —O— and form a ring with the carbon atoms to which they are attached; R 6 is alkyl, R 5 -phenyl, R 5 -phenylalkyl, thienyl, pyridyl, cycloalkyl, alkyl-OC(O)—NH—(C 1 –C 6 )alkyl-, dialkyl-aminomethyl, or R 9 is 1–2 groups independently selected from hydrogen, alkyl, hydroxy, alkoxy, halogen, —CF 3 and alkoxy-alkoxy; R 10 is 1 to 5 substituents independently selected from the group consisting of hydrogen, halogen, alkyl, hydroxy, alkoxy, —CN, —NH 2 , alkylamino, dialkylamino, —CF 3 , —OCF 3 and —S(O) 0-2 alkyl; R 12 is H or alkyl; and R 13 is alkyl-C(O)— or alkyl-SO 2 —; comprising a) reacting the hydroxyl group of a pryazole of formula II with an activating agent in the presence of a base to obtain a compound of formula III wherein L is a leaving group, and coupling the compound of formula III with a compound of formula IV Z—Y—H IV in the presence of a base to obtain a compound of formula V b) treating the compound of formula V with trialkyl orthoformate in the presence of a catalytic amount of an acid to obtain a compound of formula VI wherein R 7 is alkyl; c) condensing the compound of formula VI with a hydrazide of formula VII H 2 NHN—C(O)—R VII in the presence of an acid to obtain a compound of formula VIII and hydrolyzing the compound of formula VIII to obtain a compound of formula IX d) cyclizing the compound of formula IX with a cyanating agent selected from the group consisting of cyanates and cyanogen halides in the presence of a base.