反应详情

tert-Butyl (2S,4S)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-[3-chloro-4-fluoro-anilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate (1.13 g) was dissolved in trifluoroacetic acid (50 ml) and stirred at room temperature for 72 hours. The reaction mixture was then concentrated in vacuo, and excess water was added, followed by the careful addition of saturated aqueous sodium hydrogen carbonate. The mixture was extracted with 3% methanol in DCM and the organic layer was separated, dried (Na2SO4) and concentrated in vacuo to leave a pink solid. Trituration with cold acetonitrile gave (3S,5S)-5[({4-[3-chloro-4-fluoroanilino]-7-methoxy-quinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol as a brown solid (380 mg, 51%); NMR spectrum (DMSO-d6) 10.38-10.54 (br s, 1H), 8.52 (s, 1H), 8.36 (dd, 1H), 7.94-7.99 (m, 1H), 7.43 (t, 1H), 6.84 (d, 1H), 6.79 (d, 1H), 4.75 (d, 1H), 4.41 (dd, 1H), 4.26-4.34 (m, 1H), 4.17 (t, 1H), 3.94 (s, 3H), 3.54-3.73 (m, 1H), 2.96 (dd, 1H), 2.79 (dd, 1H), 2.11-2.20 (m, 1H), 1.41-1.49 (m, 1H); Mass spectrum MH+ 419.

1. concentrationThe reaction mixture was then concentrated in vacuo, and excess water
2. additionwas added
3. additionfollowed by the careful addition of saturated aqueous sodium hydrogen carbonate
4. extractionThe mixture was extracted with 3% methanol in DCM
5. customthe organic layer was separated
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated in vacuo
8. customto leave a pink solid