Hydrochloric Acid → 3-Methoxymethyl-1-{2-[4-(4-pyrimidin-2-yl-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-acetyl}-pyrrolidine-3-carboxylic acid [3-(2-cyclopropyl-pyridin-4-yl)-1-trityl-1H-indazol-5-yl]-amide

Participants

Reaction Steps

3-Methoxymethyl-1-{2-[4-(4-pyrimidin-2-yl-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-acetyl}-pyrrolidine-3-carboxylic acid methyl ester (500 mg, 1.11 mmol) was added to a solution of 10 ml of 50% methanol/dichloromethane. 5 mL of 1N NaOH was added and the reaction mixture stirred for 18 hrs. 5.5 ml of 1N HCl was added and the reaction mixture evaporated to dryness. To the crude reaction mixture was added 3-(2-Cyclopropyl-pyridin-4-yl)-1-trityl-1H-indazol-5-ylamine (601 mg, 1.22 mmol), HATU (464 mg, 6.66 mmol), triethylamine (0.93 ml, 6.66 mmol) and 10 ml of 50% N,N-dimethylformamide/dichloromethane. The reaction mixture was stirred for 18 hrs. followed by washing with brine and extracted with ethylacetate 3×. After evaporation of the organic layers, the crude reaction mixture was chromatographed on silica gel using 1-3% 2N NH3/methanol/dichlormethane as the eluent to obtain 570 mg of title product.

Provenance & Evidence