反应详情

Alternatively, a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene hydrochloride (66 mg, 0.12 mmol), in DCM (1 mL), methanol (1 mL) and TEA (0.07 mL) was treated with N,N-dimethyl-2-chloroacetamide (17 mg, 0.14 mmol) and TBAI (5 mg) and then stirred at RT for 48 h then 30° C. for 18 h. The reaction mixture was concentrated in vacuo and the residue partitioned between DCM and water. The aqueous layer was extracted three times with DCM the 10% methanol in DCM, the combined organic extracts dried using a phase separation cartridge before being concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0 to 10% methanol in DCM) to give 278 as a white solid (34 mg, 61%). LCMS: RT=2.26 min, [M+H]+ 465. 1H NMR 400 MHz (DMSO-d6) δ: 9.43 (1H, s), 7.96 (1H, s), 7.92 (1H, s), 6.91 (1H, s), 5.91-5.90 (1H, m), 4.60-4.58 (4H, m), 3.15 (2H, s), 3.06 (3H, s), 2.93 (2H, d, J=11.06 Hz), 2.82 (3H, s), 2.63 (1H, m), 2.15-2.14 (2H, m), 1.82-1.69 (4H, m), 1.50 (6H, d, J=6.60 Hz)

1. wait30° C. for 18 h
2. concentrationThe reaction mixture was concentrated in vacuo
3. customthe residue partitioned between DCM and water
4. extractionThe aqueous layer was extracted three times with DCM the 10% methanol in DCM
5. customthe combined organic extracts dried
6. customa phase separation cartridge
7. concentrationbefore being concentrated in vacuo