反应详情

A solution of (4S)-4-[(4-amino-1-piperidinyl)methyl]-3,8-difluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one (E1 enantiomer) (180 mg, 0.536 mmol) and [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (89 mg, 0.536 mmol) (for a synthesis, see WO2004058144, Example 61) in chloroform/methanol (5 ml/0.5 ml) was stirred at room temperature under argon for 1 h before treatment with sodium triacetoxyborohydride (341 mg, 1.608 mmol). After 1 h stirring the reaction mixture was treated with saturated sodium bicarbonate (20 ml). The aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 ml). The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was chromatographed eluting with a 0-20% gradient of methanol in dichloromethane to yield 82 mg initially and 13 mg by re-chromatographing mixed fractions of the free base of the title compound as a yellow solid (95 mg, 36%).

1. extractionThe aqueous layer was extracted with a 10% solution of methanol in dichloromethane (3×200 ml)
2. dry with materialThe combined organic extracts were dried over magnesium sulphate
3. customevaporated
4. customThe residue was chromatographed
5. washeluting with a 0-20% gradient of methanol in dichloromethane
6. customto yield 82 mg initially