Reaction Steps
2,4,5-Trichloropyrimidine (1.0 g, 5.4 mmol), 4-amino-3-methoxy-N-propylbenzamide (778 mg, 3.74 mmol), and N,N-diisopropylethylamine (1.19 g, 9.21 mmol) were combined in isopropanol (40 mL) and reacted in a microwave (120° C.) for 5½ hours. The 4-(2,5-dichloropyrimidin-4-ylamino)-3-methoxy-N-propylbenzamide that formed as a yellow solid (1.33 g, 71%) was isolated by filtration. A small amount of this material (50 mg, 0.10 mmol) was combined with 7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamine (35 mg, 0.14 mmol) and 10-camphorsulfonic acid (36 mg, 0.15 mmol) in isopropanol (3 mL) to which had been added 0.05 mL water. The mixture was heated in a microwave (130° C.) for 3 hours and on cooling was concentrated. The organics were extracted into dichloromethane which was washed with saturated sodium bicarbonate solution and subsequently dried (sodium sulfate). Concentration followed by ISCO chromatography (gradient elution: 1 to 10% MeOH:dichloromethane) afforded 4-[5-Chloro-2-(7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-3-methoxy-N-propyl-benzamide as a white solid (58 mg, 70%). Mp: 193-7° C. (dec). LCMS (m/e) 565 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.58 (d, J=8 Hz, 1H), 8.11 (s, 1H), 8.05 (s, 1H), 7.50 (s, 1H), 7.35 (s, 1H), 7.31 (m, 1H), 7.25 (m, 1H), 7.10 (d, J=8 Hz, 1H), 6.96 (s, 1H), 6.11 (m, 1H), 4.03 (s, 3H), 3.72 (m, 4H), 3.48 (m, 2H), 2.86 (m, 2H), 2.70 (m, 2H), 2.57 (s, 4H), 2.10 (m, 2H), 1.68 (m, 3H), 1.47 (m, 2H), 1.03 (t. J=7 Hz, 3H).
