反应详情

To a suspension of 2.9 g (7.2 mmol) 6-(2-chloro-pyrimidin-4-ylamino)-2,3-dihydro-benzo[1,4]dioxine-5-sulfonic acid amide and 2.0 g 4,N3-dimethyl-benzene-1,3-diamine (compound of Example 102f)) in 50 ml isopropanol is added 5 ml conc. HCl and the reaction mixture is heated to reflux for 2 hours. Then the reaction mixture is partitioned between 1 l ethyl acetate and 1 l water. The aqueous layer is adjusted to slightly basic pH by adding NaHCO3. The water layer is extracted a second time with 300 ml ethyl acetate, the combined organic phases are dried with Na2SO4 and evaporated. The crude product is purified by chromatography on silica gel eluting with ethyl acetate to give in the order of elution a mixture of the two starting materials and the title compound. The mixture of starting materials is again subjected to the reaction conditions and workup giving another 1.21 g (37% yield) of desired product.

1. temperaturethe reaction mixture is heated
2. temperatureto reflux for 2 hours
3. customThen the reaction mixture is partitioned between 1 l ethyl acetate and 1 l water
4. additionby adding NaHCO3
5. extractionThe water layer is extracted a second time with 300 ml ethyl acetate
6. dry with materialthe combined organic phases are dried with Na2SO4
7. customevaporated
8. customThe crude product is purified by chromatography on silica gel eluting with ethyl acetate
9. customto give in the order of elution
10. additiona mixture of the two starting materials