Chloroacetyl chloride → HCID 11455072, compound

Participants

Reaction Steps

Chloroacetyl chloride (21 μl) was added in one portion to a stirred solution of N-(3-chloro-4-fluorophenyl)-7-methoxy-5-[(2S)-pyrrolidin-2-ylmethoxy]-quinazolin-4-amine (96 mg) (obtained as described in Example 1, preparation of starting materials) and N,N-diisopropylethylamine (83 μl) in DCM (3 ml) at room temperature. The reaction mixture was stirred for 40 minutes and then pyrrolidine (80 μl) was added in one portion and the reaction mixture was stirred for 15 hours 30 minutes under a nitrogen atmosphere. The reaction mixture was diluted with DCM (10 ml) and washed with saturated aqueous sodium hydrogen carbonate and water. The organic layer was dried (MgSO4) and concentrated in vacuo to leave a yellow oil, which was purified by column chromatography using 0-10% methanol in DCM as eluent to give the title compound as a white solid (75 mg, 61%); NMR Spectrum (DMSO-d6) 9.90 (s, 1H), 8.40 (s, 1H), 8.10 (dd, 1H), 7.72-7.62 (m, 1), 7.39 (t, 1H), 6.82 (d, 1H), 6.78 (d, 1H), 4.62-4.54 (m, 1H), 4.34 (dd, 1H), 4.16 (dd, 1H), 3.90 (s, 3H), 3.58-3.48 (m, 2H), 3.28-3.16 (m, 2H), 2.48 (br s, 4H), 2.10-1.82 (m, 4H), 1.6 (br s, 4H); Mass spectrum MH+ 514.

Provenance & Evidence