Reaction Steps
To a solution of (3-{[tert-butyl(diphenyl)silyl]oxy}cyclobutylidene)acetonitrile (4.0 g, 8.7 mmol, from Step 4 of Example 1a) and 4-(1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (1.50 g, 4.77 mmol, US 20090181959) in acetonitrile (10 mL, 200 mmol) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.68 mL, 4.6 mmol). The reaction was stirred overnight. A further portion of 1,8-diazabicyclo[5.4.0]undec-7-ene (0.7 mL, 5 mmol) was added and the reaction was allowed to continue for an additional 72 hours. Acetonitrile was removed in vacuo. Flash chromatography on silica gel, eluting with 0%-30% EtOAc/Hexanes, was used to purify product, which was obtained as a mixture of diastereomers (2 g, 60%). 1H NMR (300 MHz, CDCl3) δ 8.33 (d, J=5.0 Hz, 1H major), 8.29 (d, J=5.0 Hz, 1H minor), 8.06 (s, 1H major), 8.03 (s, 1H major), 8.00 (s, 1H minor), 7.93 (s, 1H minor), 7.70-7.31 (m, 10H major and 10H minor), 7.19 (d, J=5.0 Hz, 1H major), 7.11 (d, J=5.0 Hz, 1H minor), 6.74 (d, J=3.6 Hz, 1H major), 6.63 (d, J=3.7 Hz, 1H minor), 5.71 (s, 2H major), 5.69 (s, 2H minor), 4.49-4.39 (m, 1H minor), 4.33 (tt, J=7.0, 7.0 Hz, 1H major), 3.67-3.45 (m, 2H major and 2H minor), 3.22 (s, 2H minor), 3.11-2.95 (m, 2H minor), 2.92-2.77 (m, 6H major), 2.65-2.50 (m, 2H minor), 1.08 (s, 9H minor), 1.03 (s, 9H major), 0.98-0.80 (m, 2H major and 2H minor), −0.06 (s, 9H major), −0.08 (s, 9H minor); LCMS (M+H)+: 662.1.
