Glycolic Acid → HCID 11397395, compound

Participants

Reaction Steps

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 171 mg) was added in one portion to a stirred solution of (3S,5R)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol (157 mg), N,N-diisopropylethylamine (131 μl) and glycolic acid (31 μl) in DCM (5 ml), under an atmosphere of nitrogen. The reaction mixture was stirred at room temperature for 4 hours and then diluted with DCM and saturated aqueous sodium hydrogen carbonate was added. The organic layer was separated, dried (Na2SO4) and then concentrated in vacuo to leave the crude product as a yellow waxy solid. Purification by column chromatography, using 0 to 10% methanol in DCM as eluent, gave the title compound as a white solid (144 mg, 80%); NMR spectrum (DMSO-d6) 10.17 (s, 1H), 8.53 (s, 1H), 8.14 (dd, 1H), 7.74-7.69 (m, 1H), 7.47 (t, 1H), 6.92 (d, 1H), 6.83 (d, 1H), 5.14-5.10 (m, 1H), 4.71-4.67 (m, 1H), 4.50-4.44 (m, 1H), 4.40-4.38 (m, 1H), 4.28-4.23 (m, 1H), 4.06-4.03 (m, 2H), 3.95 (s, 3H), 3.53-3.48 (m, 2H), 2.05-2.02 (m, 2H); Mass spectrum MH+ 477.

Provenance & Evidence