Hydrochloric Acid → HCID 178446270, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)pyrimidine-5-carboxylate (Example 1.4, step A) (0.220 g, 0.496 mmol) in anhydrous tetrahydrofuran (8 mL) was added 2M LiOH (8 mL) slowly at 0° C. The mixture was heated to 50° C. and stirred for 48 hours. The mixture was neutralized with 1N HCl and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in N,N-dimethylformamide (20 mL) and 1,1′-carbonyldiimidazole (123 mg, 0.757 mmol) and diisopropylethylamine (113 mg, 0.873 mmol) were added. The mixture was stirred for 30 minutes at 80° C. 5-Aminotetrazole (148 mg, 1.75 mmol) was then added to the reaction mixture. The resulting mixture was stirred overnight at 80° C. The mixture was quenched with water and extracted with ethyl acetate (3×10 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by preparative HPLC gave (+/−)-2-(3-methyl-1-(4′-(trifluoromethyl)biphenyl-4-yl)butylamino)-N-(1H-tetrazol-5-yl)pyrimidine-5-carboxamide (11 mg, 3.8%) as a white solid. 1H NMR (400 MHz, CD3OD, δ): 8.87 (s, 2H), 7.78 (d, 2H), 7.26 (d, 2H), 7.64 (d, 2H), 7.51 (d, 2H), 5.32-5.26 (m, 1H), 1.95-1.89 (m, 1H), 1.78-1.65 (m, 2H), 1.01 (d, 3H), 0.99 (d, 3H) ppm. MS (M+1): 495.1.

Provenance & Evidence