Sodium triacetoxyborohydride → HCID 178453643, compound

HRID 1969616Notes

Reaction equation

HRID 1969616 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:4][CH2:3]1.[CH:17]1[N:21]2[C:22]3[C:28]([CH:29]=O)=[CH:27][NH:26][C:23]=3[N:24]=[CH:25][C:20]2=[N:19][N:18]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].O>O.CN(C=O)C.C1COCC1>[C:12]([O:11][C:10](=[O:16])[NH:9][CH2:8][C@H:5]1[CH2:6][CH2:7][C@H:2]([NH:1][CH2:29][C:28]2[C:22]3[N:21]4[CH:17]=[N:18][N:19]=[C:20]4[CH:25]=[N:24][C:23]=3[NH:26][CH:27]=2)[CH2:3][CH2:4]1)([CH3:13])([CH3:15])[CH3:14]

Participants

8

Reactant 4

HCID 5049666Sodium triacetoxyborohydride3×HCID 86585896Sodium bicarbonate waterHCID 136009386HCID 136009386, compoundHCID 178453642HCID 178453642, compound

Product 1

HCID 178453643HCID 178453643, compoundYield 55.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl trans-4-aminocyclohexylmethylcarbamate (0.059 g, 0.258 mmol, AMRI) was added to a mixture of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-8-carbaldehyde (0.0403 g, 0.215 mmol, Preparation #38) and THF (1.0 mL). The mixture was stirred at ambient temperature for about 90 min. Sodium triacetoxyborohydride (0.068 g, 0.32 mmol) was added. After about 3 h, DMF (0.500 mL) was added. After about 15 h, Na(OAc)3BH (0.091 g, 0.43 mmol) was added. After about 24 h, Na(OAc)3BH (0.091 g, 0.43 mmol) was added. The mixture was warmed to about 40° C. After about 22 h, the mixture was allowed to cool to ambient temperature. Saturated aqueous NaHCO3/water (1:1, 2 mL) was added. After vigorously stirring for about 1 h, the solution was diluted with water (3 mL) and then extracted with EtOAc (6×10 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified silica gel chromatography eluting with a gradient of 10-100% [(1% 7 N NH3 in MeOH) in 10% MeOH/DCM]/DCM to give tert-butyl(trans-4-((6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-8-yl)methylamino)cyclohexyl)methylcarbamate (0.0476 g, 53%): LC/MS (Table 1, Method a) Rt=1.24 min; MS m/z 400 (M+H)+.

Workup

  1. waitAfter about 3 h
  2. waitAfter about 15 h
  3. waitAfter about 24 h
  4. temperatureThe mixture was warmed to about 40° C
  5. waitAfter about 22 h
  6. temperatureto cool to ambient temperature
  7. stirringAfter vigorously stirring for about 1 h
  8. extractionextracted with EtOAc (6×10 mL)
  9. dry with materialThe combined organics were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified silica gel chromatography
  13. washeluting with a gradient of 10-100% [(1% 7 N NH3 in MeOH) in 10% MeOH/DCM]/DCM

Sources & evidence

ORD record
ord-e7c2c8ccd52f43a78391332aed26d9ea
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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