Acetic Acid → HCID 11511695, compound

Participants

Reaction Steps

(2S,4R)-N-(4-Chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide was prepared following general procedure G, substituting 1-Isopropyl-1H-indazole-5-carbonyl chloride for 4-fluorobenzoyl chloride. (1-Isopropyl-1H-indazole-5-carbonyl chloride was prepared in three steps from 1H-Indazole-5-carboxylic acid ethyl ester. 1H-Indazole-5-carboxylic acid ethyl ester was alkylated using 2-bromopropane in presence of sodium hydride in DMF at room temperature to yield the desired 1-isopropyl-1H-indazole-5-carboxylic acid ethyl ester. Ester hydrolysis using 1N sodium hydroxide in ethanol at 80° C. gave 1-Isopropyl-1H-indazole-5-carboxylic acid and subsequent treatment of this carboxylic acid with oxalyl chloride and catalytic DMF afforded 1-isopropyl-1H-indazole-5-carbonyl chloride in decent yield). The rest of the procedures were followed as indicated in general procedure G to afford (2S,4R)-N-(4-Chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide. (The first exception being in the deprotection of the benzyloxycarbonyl group by treatment with 30% HBr in AcOH substituting for palladium on carbon (10%) and the other in the step of N-arylation of (2S,4R)-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(1-isopropyl-1H-indazol-5-yl)-methanone with 4-chlorophenylboronic acid, in presence of copper acetate, triethylamine was substituted for pyridine, and the reaction was carried out in dichloromethane at room temperature to afford the (2S,4R)-N-(4-chloro-phenyl)-N-[1-(1-isopropyl-1H-indazole-5-carbonyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-acetamide).

Provenance & Evidence