反应详情

Cyclopropylamine (Aldrich; 150 μL, 2.18 mmol), N-(2,4-dichloropyrimidin-5-yl)-N-methyl-prop-2-enamide (Intermediate 113; 337 mg, 1.45 mmol) Triethylamine (404 μL, 2.9 mmol), Titanium Tetra-ethoxide (152 μL, 0.725 mmol) and DCM (5 mL) were combined and stirred at room temp for 1 hr, heated at 40° C. for 4 hrs then cooled to room temperature. The reaction mixture was washed with water then gravity filtered through a PTFE cup, the aqueous layer containing the titanium emulsion was washed with further DCM (3×10 mL) and the combined organic solutions gravity filtered through a PTFE cup and solvents evaporated. The residue was dissolved in DCM and purified by chromatographic separation on silica eluting with a shallow gradient (25 column volumes) of 10-50% Ethyl Acetate/iso-hexane. Product containing fractions were combined and evaporated to give the title compound as a cream solid (42 mg, 11%)

1. temperatureheated at 40° C. for 4 hrs
2. temperaturethen cooled to room temperature
3. washThe reaction mixture was washed with water
4. filtrationgravity filtered through a PTFE cup
5. additionthe aqueous layer containing the titanium emulsion
6. washwas washed with further DCM (3×10 mL)
7. filtrationthe combined organic solutions gravity filtered through a PTFE cup and solvents
8. customevaporated
9. dissolutionThe residue was dissolved in DCM
10. custompurified by chromatographic separation on silica eluting with a shallow gradient (25 column volumes) of 10-50% Ethyl Acetate/iso-hexane
11. additionProduct containing fractions
12. customevaporated