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

HRID 1943196Notes

Reaction equation

HRID 1943196 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@H:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[N:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1.S1C2C=C(C=O)N=CC=2OC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.CO>[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@@H:9]2[N:19]3[C:20]4[N:11]([C:12](=[O:22])[CH:13]=[CH:14][C:15]=4[N:16]=[CH:17][C:18]3=[O:21])[CH2:10]2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 58200877(2R)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneHCID 59254367[1,3]Oxathiolo[5,4-c]pyridine-6-carbaldehyde

Product 1

HCID 66658295(2S)-2-[(4-Amino-1-piperidinyl)methyl]-1,2-dihydro-3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dioneYield 70%

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Procedure

(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%)

Workup

  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

Sources & evidence

ORD record
ord-c4558dd90fd34a3895380e3ebb822b36
Source dataset
uspto-grants-2013_03
Patent number
US08389524B2

Reaction notes

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