反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 110 °C
PROCEDURE
实验过程
5-Bromo-6-morpholino-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 18.1, 100 mg, 0.224 mmol), 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (125 mg, 0.448 mmol), Pd(Ph3P)4 (25.9 mg, 0.022 mmol) and K3PO4 (190 mg, 0.896 mmol) and toluene (1.121 mL) were added to a MW vial, which was sealed, evacuated/purged with argon and the RM was stirred for 16 h at 110° C. The RM was diluted with DME (2 mL), treated with Si-Thiol (Silicycle, 1.44 mmol/g, 93 mg, 0.134 mmol), centrifuged, the supernatant was filtered and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 10% to 60% EtOAc). The fractions containing pure product were combined and the solvent was evaporated off under reduced pressure to give a residue which was treated with TFA (500 μL, 6.49 mmol) and DCM (1.5 mL) and then stirred at RT for 4.5 h. The RM was diluted with DCM (30 mL) and washed with water, sat. aq. NaHCO3, brine and dried over Na2SO4. The solvent was evaporated off under reduced pressure to give a crude product which was purified by preparative SFC (Column Diol, from 20% to 25% in 6 min) to yield the title product as a white solid. UPLC-MS (Condition 3) tR=1.0 min, m/z=434.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.07-3.25 (m, 4H) 3.55-3.75 (m, 4H) 6.62-6.82 (m, 1H) 7.36 (d, J=8.53 Hz, 2H) 7.54-7.88 (m, 1H) 7.85-7.92 (m, 2H) 8.20-8.40 (m, 1H) 8.76 (d, J=2.13 Hz, 1H) 10.44 (br. s, 1H) 13.02-13.31 (m, 1H).
WORKUP
后处理
- customwas sealed
- customevacuated/purged with argon
- additionThe RM was diluted with DME (2 mL)
- filtrationthe supernatant was filtered
- customthe solvent was evaporated off under reduced pressure
- customto give a residue which
- customwas purified by flash chromatography (RediSep® Silica gel column, 4 g, cyclohexane/EtOAc from 10% to 60% EtOAc)
- additionThe fractions containing pure product
- customthe solvent was evaporated off under reduced pressure
- customto give a residue which
- stirringstirred at RT for 4.5 h
- washwashed with water, sat. aq. NaHCO3, brine
- dry with materialdried over Na2SO4
- customThe solvent was evaporated off under reduced pressure
- customto give a crude product which
- customwas purified by preparative SFC (Column Diol, from 20% to 25% in 6 min)