反应详情

(2E)-4-Bromobut-2-enoic acid (1.33 g, 6.83 mmol) was dissolved in petroleum ether (25 mL). Thionylchloride (2.65 mL, 36.6 mmol) was added, and the mixture was heated to reflux for 4 h. The mixture was then concentrated in vacuo. Toluene was added and again removed in vacuo. The residue was dissolved in dichloromethane (14 mL). This solution was added to a solution of N-(3,4-dichlorophenyl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4-amine from Example 15A (2.00 g, 5.69 mmol) and DIPEA (1.25 g, 9.68 mmol) in DMF (20 mL) at −10° C. The mixture was warmed to rt and stirred overnight. The precipitate was collected by suction filtration and washed with water to yield 1.52 g of a solid, which was used in the next step without further purification or separation.

1. temperaturethe mixture was heated
2. temperatureto reflux for 4 h
3. concentrationThe mixture was then concentrated in vacuo
4. additionToluene was added
5. customagain removed in vacuo
6. dissolutionThe residue was dissolved in dichloromethane (14 mL)
7. filtrationThe precipitate was collected by suction filtration
8. washwashed with water