Triethylamine → N-[(1R,2R)-2-(2,5-dichloropyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

(1R,2R)-Cyclohexane-1,2-diamine (4.17 g, 36.5 mmol) was added into a round bottom flask and was dissolved in tetrahydrofuran (200 mL). The flask was cooled at 0° C., then 2,4,5-trichloropyrimidine (6.08 g, 33.1 mmol) was added. A precipitate formed, and the reaction was stirred 5 min before triethylamine (12 mL, 83 mmol) and methanesulfonyl chloride (4.00 mL, 51.7 mmol) were added simultaneously via two syringes. After 5 min, external cooling was removed, and the contents were stirred under an atmosphere of nitrogen. After 45 min, the contents were partitioned between dichloromethane (150 mL) and saturated sodium bicarbonate solution (150 mL). The layers were separated, and the aqueous phase extracted with dichloromethane (100 mL). The organic fractions were washed with brine (100 mL), dried (sodium sulfate) and were concentrated onto 37 g silica gel, and chromatographed on an ISCO cartridge (120 g SiO2, 0-50% EA:Hex). N-[(1R,2R)-2-(2,5-Dichloro-pyrimidin-4-ylamino)-cyclohexyl]-methanesulfonamide was isolated as a white solid (4.8 g, 43%). m.p. 163-166° C.; LCMS (m/e) 339 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.91 (d, 1H, J=7.6 Hz), 5.91 (d, 1H, J=7.6 Hz), 5.91 (d, 1H, J=7.6 Hz), 3.32 (m, 1H), 3.91 (m, 1H), 2.92 (s, 3H), 2.25 (d, 1H, J=12 Hz), 2.13 (d, 1H, J=12 Hz), 1.83 (m, 2H), 1.25-1.48 (m, 4H).

Provenance & Evidence