Cl[C:2]1[C:3]2[N:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][C@@H:22]4[CH2:26][CH2:27][CH2:28][C@@H:21]34)[N:17]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]3)[C:4]=2[C:5]([C:10]2[CH:11]=[N:12][CH:13]=[C:14]([Cl:16])[CH:15]=2)=[N:6][C:7]=1[C:8]#[N:9].[F-].[Cs+].[CH3:39][NH:40][CH3:41].CS(C)=O>C1COCC1.CCOC(C)=O>[Cl:16][C:14]1[CH:15]=[C:10]([C:5]2[C:4]3[N:17]([CH2:29][C@H:30]4[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]4)[C:18]([N:20]4[CH2:25][CH2:24][O:23][C@@H:22]5[CH2:26][CH2:27][CH2:28][C@@H:21]45)=[N:19][C:3]=3[C:2]([N:40]([CH3:41])[CH3:39])=[C:7]([C:8]#[N:9])[N:6]=2)[CH:11]=[N:12][CH:13]=1A dry vial, under an atmosphere of nitrogen, was charged with 7-chloro-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 11.2, step 1; 50 mg, 0.095 mmol), CsF (101 mg, 0.666 mmol), dimethylamine (0.476 mL of a 2M solution in THF, 0.952 mmol) and DMSO (1 mL). The vial was sealed and heated to 100° C. for 8 hours. The reaction was cooled to room temperature, diluted with EtOAc (25 mL) and washed with water (5 mL) and brine (5 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was purified on a silica gel column with 0 to 100% EtOAc/hexanes to afford 4-(5-chloropyridin-3-yl)-7-(dimethylamino)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C29H36ClN7O [M+H]+=534. found=534.
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