反应详情

N-{2-[(4-Chloroquinazolin-5-yl)oxy]ethyl}-N-methylacetamide (38 mg, 0.136 mmol) and 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (obtained as described in Example 103, preparation of stating materials, 32 mg, 0.150 mmol) were dissolved in iso-propanol, and the mixture heated to reflux for 1 hour. The mixture was concentrated in vacuo, and the residue purified by chromatography, eluting with 0 to 5.5% (10:1 methanol/conc. NH3(aq)) in ethyl acetate. Evaporation of the appropriate fractions gave N-methyl-N-(2-{[4-({3-methyl-4-[(6-methylpyridin-3-yl)oxy]phenyl}amino)quinazolin-5-yl]oxy}ethyl)acetamide as a dry film (24 mg, 39%); NMR Spectrum (DMSO-d6, 400 MHz), 373K 1.96 (s, 3H), 2.24 (s, 3H), 2.46 (s, 3H), 2.94 (s, 3H), 3.90 (t, 2H), 4.50 (t, 3H), 6.94 (d, 1H), 7.18 (d, 1H), 7.21 (m, 2H), 7.36 (d, 1H), 7.63 (dd, 1H), 7.68 (d, 1H), 7.71 (dd, 1H), 8.17 (dd, 1H), 8.47 (s, 1H), 9.76 (s, 1H); Mass spectrum MH+ 458.4.

1. temperaturethe mixture heated
2. temperatureto reflux for 1 hour
3. concentrationThe mixture was concentrated in vacuo
4. customthe residue purified by chromatography
5. washeluting with 0 to 5.5% (10:1 methanol/conc. NH3(aq)) in ethyl acetate
6. customEvaporation of the appropriate fractions