Reaction Steps
A mixture of 0.41 g (0.84 mmol) of 6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-4-(4-morpholinyl)-1-(4-piperidinyl)-1H-pyrazolo[3,4-d]pyrimidine (Example 8) and 0.27 g (2 mmol) DIPEA in CH2Cl2 was cooled to −15° C., and 200 mg (1.2 mmol) of 2-chloroethanesulfonyl chloride was added. The mixture was allowed to warm to 0° C. over 1 hr, and water was added. The organic layer was dried and concentrated. Chromatography on silica, eluting with CH2Cl2/EtOAc (1:1), gave 216 mg (45% yield) of 6-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-4-(4-morpholinyl)-1-[1-(vinylsulfonyl)-4-piperidinyl]-1H-pyrazolo[3,4-d]pyrimidine: mp (CH2Cl2-MeOH) 243-246° C.; 1H NMR (CDCl3) δ 8.00 (s, 1H), 7.81 (dd, J=8.4, 0.7 Hz, 1H), 7.44 (t, JHF=53.5 Hz, 1H), 7.37 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 6.51 (dd, J=16.6, 9.9 Hz, 1H), 6.29 (d, J=16.6 Hz, 1H), 6.07 (d, J=9.9 Hz, 1H), 4.81 (tt, J=11.2, 4.1 Hz, 1H), 4.07 (s, 3H), 4.06 (m, 4H), 3.96 (m, 1H), 3.91 (m, 4H), 3.88 (m, 1H), 2.95 (dt J=12.4, 2.6 Hz, 2H), 2.43 (ddd, J=24.5, 11.8, 4.2 Hz, 2H), 2.14 (dd, J=11.8, 4.2 Hz, 2H); Anal. Calcd. for C25H28F2N8O4S: C, 52.3; H, 4.9; N, 19.5. Found: C, 52.3; H, 4.7; N, 19.8%.
