反应详情

Glycolic acid (22 mg) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 110 mg) were added sequentially, each in one portion, to a stirred solution of N-(3-chloro-4-fluorophenyl)-7-ethoxy-5-[(2R)-pyrrolidin-2-ylmethoxy]-quinazolin-4-amine (81 mg) and N,N-diisopropylethylamine (68 μl) in DCM (2.5 ml) at room temperature. The reaction mixture was stirred for 16 hours and then concentrated in vacuo to leave a brown residue. The residue was taken up in a 7:2:1 mixture of DMSO:acetonitrile:water, filtered and then purified by reverse phase HPLC. The fractions containing the required product were combined, basified by the addition of potassium carbonate and then extracted with DCM. The organic layer was dried (MgSO4) and then concentrated in vacuo to give the title compound as a white solid (36 mg, 39%); NMR Spectrum (DMSO-d6 at 373 K) 9.80 (br s, 1H), 8.40 (s, 1H), 8.15 (m, 1H), 7.65 (m, 1H), 7.33 (m, 1H), 6.80 (m, 2H), 4.60 (m, 1H), 4.50 (m, 1H), 4.30-4.10 (m, 4H), 4.0 (m, 2H), 3.50-3.40 (m, 2H), 2.10-1.85 (m, 4H), 1.40 (t, 3H); Mass spectrum MH+ 475.

1. customat room temperature
2. concentrationconcentrated in vacuo
3. customto leave a brown residue
4. filtrationacetonitrile:water, filtered
5. custompurified by reverse phase HPLC
6. additionThe fractions containing the required product
7. additionbasified by the addition of potassium carbonate
8. extractionextracted with DCM
9. dry with materialThe organic layer was dried (MgSO4)
10. concentrationconcentrated in vacuo