1-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine → 2-tert-Butyl-4-({1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}amino)-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Participants

Reaction Conditions

Reaction Steps

2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (200 mg, 0.667 mmol) was dissolved in dry DMF (2 mL) under nitrogen atmosphere. 1-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine (188 mg, 0.674 mmol) was added followed by TEA (68 mg, 0.667 mmol) and the reaction mixture was heated in a microwave reactor at 120° C. for 20 mins. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3-solution, dried over Na2SO4, filtered and evaporated. The crude product was purified on a Biotage Horizon HPFC system using Heptane and EtOAc as eluant affording the title compound (284 mg, 77.6%). 1H NMR (500 MHz, CDCl3): δ 1.46-1.54 (m, 2H), 1.73-1.79 (m, 1H), 2.51 (t, 2H), 3.12-3.19 (m, 1H), 3.79-3.82 (m, 2H), 5.28 (d, 1H), 7.44-7.46 (m, 3H), 7.53-7.55 (m, 2H), 7.72 (s, 1H), 8.33 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 27.82, 32.36, 47.43, 50.27, 61.80, 107.32, 120.35 (q, J=33.4 Hz), 121.28, 123.48 (q, J=271.3 Hz), 125.36, 128.94, 130.17, 131.85, 134.16, 136.15, 143.10, 159.87, 160.06; Mass Spectrum: M+H+ 543.1.

Provenance & Evidence