反应详情

(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (50 mg, 0.166 mmol) (for a preparation see Example 16(j)) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carboxaldehyde (29 mg, 0.90 eq.) (for a synthesis see WO2003087098, Example 301(d)) were stirred in 9:1 chloroform:methanol (1 ml) at room temperature for 3 hours, then sodium triacetoxyborohydride (105 mg, 3.00 eq.) was added. The mixture was stirred at room temperature for a further 30 minutes, then saturated aqueous sodium hydrogen carbonate (0.5 ml) was added, and the organic phase was diluted with DCM (10 ml). The mixture was stirred vigorously for 10 minutes, then the organic phase was separated (hydrophobic frit) and evaporated under reduced pressure. The residue was taken up in DCM (ca. 3 ml)+1 drop MeOH and purified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM). Appropriate fractions were combined and evaporated to give the free base of the title compound as a yellow amorphous solid.

1. stirringThe mixture was stirred vigorously for 10 minutes
2. customthe organic phase was separated (hydrophobic frit)
3. customevaporated under reduced pressure
4. custompurified by column chromatography on silica (eluted with 0-12% (2M NH3 in MeOH) in DCM)
5. customevaporated