(1-(氨基甲基)环己基)甲醇

反应条件: temp:125.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 4:1 mixture of 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfinyl)benzo[d]thiazole and 6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)-2-(methylsulfonyl)benzo[d]thiazole (80 mg) from Step 2 of Example 63 was dissolved in anhydrous DMA (2 mL), and (1-(aminomethyl)cyclohexyl)methanol (175 mg, 1.22 mmol) from Step 1 of this Example and DIEA (157 mg, 1.22 mmol) were added. The reaction vessel was sealed and the mixture was heated with stirring at 125° C. for 15 h. After cooling to rt, the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase to afford 1-(((6-((3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)methyl)cyclohexanol (22 mg) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.60 (s, 1H), 8.38 (dd, J=1.1, 4.7 Hz, 1H), 8.09 (dd, J=1.3, 7.9 Hz, 1H), 7.99 (t, J=5.7 Hz, 1H), 7.68 (s, 1H), 7.20-7.33 (m, 3H), 5.49 (s, 2H), 3.33 (d, J=5.8 Hz, 2H), 3.21 (s, 1H), 1.21-1.49 (m, 12H). LCMS (ESI) m/z 408 (M+H)+. The reaction vessel was sealed the mixture was heated After cooling to rt the mixture was purified directly by reverse-phase a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of methyl 1-cyanocyclohexanecarboxylate (2 g, 11.96 mmol) in anhydrous THF (40 mL) at rt was added portionwise LiAlH4 (1.36 g, 35.88 mmol). The reaction vessel was sealed and the mixture was heated at 80° C. for 5 h. The mixture was cooled to 0° C. and water (1 mL), 1M aq NaOH (1 mL), and water (3 mL) were added sequentially. To the resulting mixture were added DCM and saturated aq sodium potassium tartrate, and the mixture was stirred for 3 h. The organic layer was separated and further washed with brine. The organic layer was separated, dried over MgSO4, filtered, and concentrated under reduced pressure to afford (1-(aminomethyl)cyclohexyl)methanol (1 g) which was not purified further. LCMS (ESI) m/z 144 (M+H)+. The reaction vessel was sealed The mixture was cooled to 0° C. The organic layer was separated further washed with brine The organic layer was separated dried over MgSO4 filtered concentrated under reduced pressure