反应详情

A solution of tert-butyl 4-chloro-2-fluoro-3-((4-((3-(trifluoromethyl)phenyl)amino)quinazolin-8-yl)carbamoyl)benzylcarbamate (Intermediate-16, 80 mg, 0.135 mmol) in HCl in MeOH (2 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and the concentrate was dissolved in DMF (1 mL). The solution was treated with DIPEA (87 mg, 0.675 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (119 mg, 0.27 mmol) followed by (S)-(−)-tetrahydro-2-furoic acid (24 mg, 0.203 mmol) at rt. The reaction mixture was stirred for 2 h before it was diluted with EtOAc and was washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 35 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 10.67 (s, 1H), 10.14 (s, 1H), 8.79 (d, 1H), 8.71 (s, 1H), 8.47 (br t, 1H), 8.37 (m, 2H), 8.25 (d, 1H), 7.73-7.65 (m, 2H), 7.50 (d, 1H), 7.39 (m, 2H), 4.33 (m, 3H), 3.94 (m, 1H), 3.80 (m, 1H), 2.14 (m, 1H), 1.84 (m, 3H); MS (m/z): 588.34 (M+H)+.

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe concentrate was dissolved in DMF (1 mL)
3. washwas washed with H2O and brine
4. customThe organic layer was separated
5. customdried
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by column chromatography