Reaction Steps
(S)-3-(7-Amino-8-methoxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)-1,1,1-trifluoro-propan-2-ol (88 mg, 0.29 mmol), (1S,2S,3R,4R)-3-(2,5-Dichloro-pyrimidin-4-ylamino)-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide (89 mg, 0.30 mmol), and 10-Camphorsulfonic acid (105 mg, 0.452 mmol) in 2-Methoxyethanol (4 mL) was heated in a microwave vial at 120° C. for 4 h. The brown solution was added dropwise to a satd. sodium bicarbonate solution (10 mL) and the vial was rinsed with 2 mL water and also added. The precipitated product was allowed to stand for 30 min, filtered and washed with water (5 mL). The crude solid was chromatographed (2×12 g silica gel, 0-80% EtOAc:Hex) to afford (1S,2S,3R,4R)-3-{5-Chloro-2-[8-methoxy-3-((S)-3,3,3-trifluoro-2-hydroxy-propyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamino]-pyrimidin-4-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide as a beige solid (73 mg, 44%). LCMS: 567 (M+H); MP=120-126° C.; 1H-NMR, CDCl3: 8.24 (s, 1H), 7.92 (s, 1H), 7.43 (s, 1H), 6.66 (s, 1H), 6.61 (d, 1H, J=7.9 Hz), 6.33 (m, 2H), 5.57 (br s, 1H), 5.29 (br s, 1H), 4.46 (m, 1H), 4.07 (m, 1H), 3.89 (s, 3H), 3.10 (br s, 1H), 2.8-3.0 (m, 9H), 2.70 (m, 3H), 2.53 (d, 1H, J=8.1 Hz), 2.28 (d, 1H, J=9.4 Hz), 1.68 (d, 1H, J=8.7 Hz).
