Ethyl Bromide → HCID 11751862, compound

Participants

Reaction Conditions

Reaction Steps

The crude tert-butyl (2R)-2-[({4-[3-chloro-4-fluoroanilino]-7-hydroxy-quinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate (120 mg) was dissolved in DMA (1 ml), and bromoethane (27 μl) and potassium carbonate (68 mg) were each added in one portion. The reaction mixture was heated at 40° C. for 16 hours and then cooled to room temperature. Trifluoroacetic acid (0.5 ml) was then added and the reaction mixture was stirred for 4 hours at room temperature. Further trifluoroacetic acid (1 ml) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was then poured onto saturated aqueous sodium hydrogen carbonate and then extracted with ethyl acetate. The organic layer was dried (MgSO4) and then concentrated in vacuo to leave a green oil. Purification by flash chromatography, using 2-5% methanol in DCM as eluent, gave the N-(3-chloro-4-fluorophenyl)-7-ethoxy-5-[(2R)-pyrrolidin-2-ylmethoxy]quinazolin-4-amine as a pale green solid (83 mg, 52% over three steps); NMR Spectrum (DMSO-d6) 10.2 (s, 1H), 9.50 (s, 1H), 8.30-8.20 (m, 1H), 7.90-7.80 (m, 1H), 7.50-7.40 (m, 1H), 6.80-6.70 (m, 1H), 4.50-4.40 (m, 1H), 4.30-4.20 (m, 1H), 4.30-4.10 (m, 3H), 3.90-3.80 (m, 1H), 3.15-3.05 (m, 2H), 2.10-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.70-1.60 (m, 1H), 1.40 (t, 3H); Mass spectrum MH+ 417.

Provenance & Evidence