Acetonitrile → (3R,5R)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol

Participants

Reaction Steps

tert-Butyl (2R,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-[3-chloro-4-fluoro-anilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate (839 mg) 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 green solid. Trituration with cold acetonitrile gave (3R,5R)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxy-quinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol as grey solid (540 mg, 98%); NMR spectrum (DMSO-d6) 10.54-10.02 (br s, 1H), 8.48 (s, 1H), 8.32 (dd, 1H), 7.93-7.88 (m, 1H), 7.38 (t, 1H), 6.79 (d, 1H), 6.69 (d, 1H), 5.05-4.74 (br s, 1H), 4.40-4.32 (m, 2H), 4.16 (t, 1H), 3.91 (s, 3H), 3.80-3.40 (br m, 21), 2.98 (dd, 1H), 2.86 (dd, 1H), 2.22-2.14 (m, 1H), 1.52-1.44 (m, 1H); Mass spectrum MH+ 419.

Provenance & Evidence