反应详情

A suspension of (2R)-2-[(4-amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (for a preparation see Example 16A(j)) (70 mg, 0.232 mmol) and 2,3-dihydrofuro[2,3-c]pyridine-5-carbaldehyde (for a synthesis see WO2007122258, Example 43(f) (34.6 mg, 0.232 mmol) in chloroform (5 ml) and methanol (0.250 ml) at room temperature under nitrogen was stirred for 0.5 h (the suspension turned into a solution). Sodium triacetoxyborohydride (155 mg, 0.697 mmol) was then added and the reaction was stirred at room temperature. After 3 h there was no starting material left so a saturated aqueous solution of sodium bicarbonate (25 mL) was added followed by 20% methanol/DCM (25 mL) and the aqueous layer was extracted and then separated from the organic layer. The aqueous layer was extracted again twice with 20% methanol/DCM (2×25 mL). The combined organic extracts were dried on sodium sulphate, filtered and evaporated to afford 90 mg of crude product. The crude product was purified by silica chromatography (0-20% MeOH/DCM) to afford the free base of the title compound as a pale yellow solid (77 mg, 76%).

1. customat room temperature
2. stirringthe reaction was stirred at room temperature
3. waitAfter 3 h there was
4. additionwas added
5. extractionthe aqueous layer was extracted
6. customseparated from the organic layer
7. extractionThe aqueous layer was extracted again twice with 20% methanol/DCM (2×25 mL)
8. customThe combined organic extracts were dried on sodium sulphate
9. filtrationfiltered
10. customevaporated
11. customto afford 90 mg of crude product
12. customThe crude product was purified by silica chromatography (0-20% MeOH/DCM)