Sodium triacetoxyborohydride → (2S)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione

(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione (100 mg, 0.332 mmol) was stirred with [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde (for a synthesis see WO2004058144 Example 61) (45 mg, 0.811 eq.) in chloroform:methanol (9:1, v:v, 5 ml) at room temperature for 2 hours; the mixture was then treated with sodium triacetoxyborohydride (211 mg, 3.0 eq.) with vigorous stirring at room temperature for 30 mins. The mixture was quenched by addition of saturated aqueous sodium hydrogen carbonate (1 ml). DCM (10 ml) was added and vigorous stirring was continued for 10 mins, followed by separation of the phases (hydrophobic frit). The organic phase was evaporated under reduced pressure and the crude product was purified by column chromatography on silica (eluting with 0-12% (2M NH3 in MeOH) in DCM). Appropriate fractions were combined and evaporated under reduced pressure and dried on the vacuum line over the weekend to give the free base of the title compound as a pale yellow foam (70 mg, 44.3%)

1. customat room temperature
2. customfor 2 hours
3. customThe mixture was quenched by addition of saturated aqueous sodium hydrogen carbonate (1 ml)
4. additionDCM (10 ml) was added
5. stirringvigorous stirring
6. waitwas continued for 10 mins
7. customfollowed by separation of the phases (hydrophobic frit)
8. customThe organic phase was evaporated under reduced pressure
9. customthe crude product was purified by column chromatography on silica (eluting with 0-12% (2M NH3 in MeOH) in DCM)
10. customevaporated under reduced pressure
11. customdried on the vacuum line over the weekend

ORD record

ord-c4558dd90fd34a3895380e3ebb822b36

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389524B2