反应详情

For the preparation of the starting material compound 65.1, please refer to the experimental procedure for Example 65. To a solution of trans-4-(morpholin-4-yl)cyclohexan-1-ol (277 mg, 1.50 mmol, 1.50 equiv) in distilled THF (20 mL) was added sodium hydride (605 dispersion in mineral oil, 200 mg, 5.00 mmol, 5.00 equiv) slowly at 0° C. under nitrogen. After stirring for 30 min at room temperature, a solution of 3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-chloro-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene (355 mg, 1.00 mmol, 1.00 equiv) in 5 mL of THF was added dropwise and the resulting solution was stirred for 6 h at ambient temperature. The reaction was quenched with NH4Cl (sat.), extracted with EtOAc (3×80 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate. After filtration and concentration in vacuo, the residue was purified by a silica gel column with EtOAc/petroleum ether (1:1-3:1) to provide 350 mg (69%) of the title 3-[[(tert-butyldimethylsilyl)oxy]methyl]-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(12),2(6),8,10-tetraene as a light yellow oil. MS: (ES, m/z): 504 [M+H]+.

1. stirringthe resulting solution was stirred for 6 h at ambient temperature
2. customThe reaction was quenched with NH4Cl (sat.)
3. extractionextracted with EtOAc (3×80 mL)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationAfter filtration and concentration in vacuo
7. customthe residue was purified by a silica gel column with EtOAc/petroleum ether (1:1-3:1)