反应详情

温度

170 °C

A mixture of 4-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (20 mg, 0.052 mmol, Intermediate-2, single enantiomer), 1-amino-2-methyl-1-oxopropan-2-yl acetate (15 mg, 0.10 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 5.2 micro mol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (9.0 mg, 0.016 mmol) and tripotassium phosphate (16 mg, 0.075 mmol) in dioxane (2 mL) is heated at 170° C. for 40 min by microwave irradiation. The reaction mixture is filtered through a short column of NH-gel eluting with EtOAc and volatiles are removed. The residue is dissolved in THF (1.0 mL) and 2 M aqueous sodium hydroxide solution (0.50 mL) is added, and the mixture is stirred overnight at rt. The mixture is neutralized by the addition of 2 M hydrochloric acid (0.50 mL), diluted with THF (4.0 mL) and extracted with EtOAc. The separated organic layer is dried over sodium sulfate and concentrated in vacuo. The mixture is purified by a strong cation exchange cartridge (BondElute™ SCX, 1 g/6 mL, Varian Inc.) and then by preparative LC-MS to give 7.2 mg (31% yield) of the title compound.

1. filtrationThe reaction mixture is filtered through a short column of NH-gel
2. washeluting with EtOAc and volatiles
3. customare removed
4. dissolutionThe residue is dissolved in THF (1.0 mL)
5. addition2 M aqueous sodium hydroxide solution (0.50 mL) is added
6. additionThe mixture is neutralized by the addition of 2 M hydrochloric acid (0.50 mL)
7. additiondiluted with THF (4.0 mL)
8. extractionextracted with EtOAc
9. dry with materialThe separated organic layer is dried over sodium sulfate
10. concentrationconcentrated in vacuo
11. customThe mixture is purified by a strong cation exchange cartridge (BondElute™ SCX, 1 g/6 mL, Varian Inc.)