Isopropyl iodide → HCID 16743761, compound

Participants

Reaction Steps

To a solution of (S)-2-fluoro-5-(1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-1-(5-methyl-4-(trifluoromethyl)thiazol-2-ylamino)-2-phenylethyl)phenol (16 mg, 0.026 mmol) in DMF (0.5 mL) was added K2CO3 (8 mg, 0.058 mmol), followed by the addition of 2-iodopropane (5 mg, 0.03 mmol). The reaction vessel was sealed and stirred at room temperature for 18 h. The solid was removed by filtration and the filtrate was purified by preparative HPLC Phenomenex AXIA Luna S5 30×75 mm Ballistic column 50-100% ACN (90% in water, 0.1% TFA) gradient over 10 min with flow rate 40 mL/min and UV detection at 220 nm. (S)-N-(1-(4-fluoro-3-isopropoxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-5-methyl-4-(trifluoromethyl)thiazol-2-amine eluted at a retention time of 10.99 min (13 mg, 77% yield). LCMS: RT=4.38 min [M+H] 649.2 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). NMR: 400 MHz 1H (CDCl3) 7.18 ppm, 1H, m; 7.11 ppm, 3H, m; 6.97 ppm, 5H, m; 6.59 ppm, 2H, d, J=7.07 Hz; 5.86 ppm, 1H, m; 4.46 ppm, 1H, m; 3.71 ppm, 2H, s; 2.29 ppm, 3H, m; 1.24 ppm, 6H, dd, J=8.84, 6.06 Hz.

Provenance & Evidence