Pyridine → 3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-amine

Participants

Reaction Conditions

Reaction Steps

(c)(d)(e)(f) 3-(1-Cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanoic acid (393 mg, 1 mmol) was dissolved in 20 mL DCM and treated with 130 mL pyridine and 127 uL of cyanuric fluoride and stirred overnight. The reaction was extracted from 1 M HCl with EtOAc×3. The combined organic layers were dried over MgSO4, filtered, concentrated, and then taken up in THF (20 mL), cooled to −78° C. and ammonia gas was bubbled in for 1 min. The reaction was allowed to warm to rt. Quantitative conversion to 3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanamide. (M+H)+=390. This compound was dissolved in 15 mL THF and treated with LiAlH4 (4 mL, 4 mmol, 1 M in THF) and stirred for 3 h. The reaction was quenched with EtOAc and then 5 mL 1 M NaOH. After stirring 30 min, the reaction was extracted from brine 4× EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give 3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropan-1-amine. (M+H)+=376. This material was dissolved in 3 mL DCM and treated with 0.2 mL trifluoroacetic anhydride. After 3 h, the reaction was rotovapped down and purified by HPLC to give N-(3-(1-cycloheptyl-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)-2,2,2-trifluoroacetamide (182 mg, 38% for four steps). (M+H)+=472.

Provenance & Evidence