反应详情

To a solution of (1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanol (the product of step iv) (0.24 g) in dry THF (10 mL) at 0° C. was added in portions sodium hydride (91 mg as 60% dispersion in mineral oil) followed in portions by 4,6-dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (the product of example 1 step ii) (0.50 g). The reaction mixture was stirred at room temperature for 48 h then quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ethyl acetate. The layers were separated and the aqueous layer extracted with further ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel using EtOAc/isohexane (1:19 to 1:9 gradient) as eluent to give the subtitle compound as a pale yellow solid. Yield: 0.42 g.

1. customthen quenched with saturated aqueous ammonium chloride (10 mL)
2. additiondiluted with ethyl acetate
3. customThe layers were separated
4. extractionthe aqueous layer extracted with further ethyl acetate
5. washThe combined organic extracts were washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customevaporated
9. customThe residue was purified by column chromatography on silica gel