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 dihydrochloride (for a preparation see Example 16A(j), amine was converted into dihydrochloride after chiral hplc purification) (51.3 mg, 0.137 mmol) in chloroform (5 ml) and methanol (0.1 ml) at rt under argon was treated with triethylamine (0.057 ml, 0.411 mmol) and stirred at rt for 0.25 h. The solution was then treated with 5-fluoro-2,3-dihydro-1,4-benzodioxin-6-carbaldehyde (24.95 mg, 0.137 mmol) and stirred for a further 0.5 h. The solution was then treated with sodium triacetoxyborohydride (174 mg, 0.822 mmol) and stirred at rt for 2 h, more sodium triacetoxyborohydride (174 mg, 0.137 mmol) was added, reaction stirred for a further 1 h, the reaction was then treated with saturated aqueous NaHCO3 (20 ml) and extracted with 20% methanol/DCM (3×20 ml). The combined organic extracts were dried (MgSO4) and chromatographed (0-20% methanol:DCM) to give the free base of the title compound as a white solid (29 mg, 0.062 mmol, 45%,).

1. customafter chiral hplc purification) (51.3 mg, 0.137 mmol) in chloroform (5 ml)
2. stirringstirred for a further 0.5 h
3. stirringstirred at rt for 2 h
4. customreaction
5. stirringstirred for a further 1 h
6. extractionextracted with 20% methanol/DCM (3×20 ml)
7. dry with materialThe combined organic extracts were dried (MgSO4)
8. customchromatographed (0-20% methanol:DCM)