反应详情

温度

80 °C

A solution of methyl 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetate dihydrochloride (17.5 g, 43.51 mmol) in dimethylacetamide (0.5M, 88 mL) was treated with 2,2,2-trichloroethyl-3-tert-butyl-1-p-tolyl-1H-pyrazol-5-ylcarbamate (17.96 g, 44.38 mmol), followed by diisopropylethylamine (30.3 mL, 174 mmol) at room temperature. The mixture was heated at 80° C. overnight. The mixture was concentrated in vacuo and the residue distributed between EtOAc and saturated aqueous NH4Cl. The organic layer was separated and washed with brine, filtered through 1PS paper, evaporated in vacuo to a brown foam. The foam was triturated in ether, and the precipitated solids were collected by filtration to provide 22.55 g (89%) of the desired compound. MS (APCI+) m/z 585 (M+1) detected. 1H NMR (400 MHz, DMSO-d6) δ 8.3 (s, 1H), 8.07 (s, 1H), 7.68 (d, 1H, J=8.9 Hz), 6.85-7.37 (m, 8H), 6.24 (s, 1H), 5.4 (s, 2H), 4.28 (d, 2H, J=5.8 Hz), 3.68 (s, 3H), 2.35 (s, 3H), 1.25 (s, 9H).

1. concentrationThe mixture was concentrated in vacuo
2. customThe organic layer was separated
3. washwashed with brine
4. filtrationfiltered through 1PS paper
5. customevaporated in vacuo to a brown foam
6. customThe foam was triturated in ether
7. filtrationthe precipitated solids were collected by filtration