反应详情

温度

-10 °C

(2E)-4-Bromobut-2-enoic acid (1.48 g, 7.17 mmol) was stirred in thionylchloride (10 mL, 137 mmol) for 4 h. The mixture was then concentrated in vacuo. Twice, 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-chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]-pyrimidin-4-amine from Example 12A (2.00 g, 5.97 mmol) and DIPEA (1.93 g, 14.9 mmol) in DMF (35 mL) at −10° C. The mixture was stirred for 1.5 h at −10° C. and subsequently for 15 h at rt. The mixture was then diluted with water. Ethyl acetate was added, and the precipitate was collected by suction filtration to yield 1.50 g of a solid, which was identified by LC/MS as a mixture of the bromo- and chloro-allylic compound. It was used in the next step without further purification or separation.

1. concentrationThe mixture was then concentrated in vacuo
2. additionTwice, toluene was added
3. customagain removed in vacuo
4. dissolutionThe residue was dissolved in dichloromethane (14 mL)
5. filtrationthe precipitate was collected by suction filtration