Reaction Steps
N*4*-((1R,2R)-2-Amino-cyclohexyl)-5-chloro-N*2*-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl]-pyrimidine-2,4-diamine was dissolved in Methylene chloride (5 mL) and Triethylamine (0.15 mL, 1.1 mmol) was added, followed by 2,2,2-Trifluoroethanesulfonyl chloride (0.025 mL, 0.23 mmol). Stir under an atmosphere of Nitrogen at room temperature for 45 min, then partition between 10 mL satd. sodium bicarbonate and 10 mL DCM. Separate and extract the aqueous layer, 3×10 mL DCM. Dry the combined organics over sodium sulfate, filter and concentrate in vacuo. The resultant oil was purified on a sulfonic acid resin cartridge, washing with methanol, eluting with ammonia/methanol. Conc. in vacuo reconcentrating from DCM afforded an oil. Subsequent purification on silica gel (0-10% MeOH:DCM, 12 g SiO2) gave 2,2,2-Trifluoro-ethanesulfonic acid ((1R,2R)-2-{5-chloro-2-[3-(2-methoxy-ethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-cyclohexyl)-amide (55 mg, 53%) as a colorless film. LCMS (m/e) 591 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 7.88 (s, 1H), 7.21 (d, 1H, J=7.9 Hz), 7.18 (s, 1H), 7.01 (d, 1H, J=7.9 Hz), 6.97 (s, 1H), 5.36 (d, 1H, J=7.5 Hz), 5.31 (s, 1H), 3.84 (m, 1H), 3.61 (q, 2H, J=9.0 Hz), 3.55 (t, 2H, J=5.4 Hz), 3.36 (s, 3H), 3.29 (m, 1H), 2.9 (m, 4H), 2.72 (m, 6H), 2.17 (m, 2H), 1.82 (m, 2H), 1.34 (m, 4H).
