Sodium triacetoxyborohydride → HCID 59496099, compound

HRID 1513331Notes

Reaction equation

HRID 1513331 reaction equation
[CH3:1][C:2]1[C:3](=[O:21])[N:4]([C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:14])[C:5](=[O:12])[N:6]([CH2:8][CH2:9][CH:10]=O)[N:7]=1.[F:22][C:23]([F:37])([F:36])[C:24]1[CH:29]=[CH:28][C:27]([C@:30]23[CH2:35][C@H:34]2[CH2:33][NH:32][CH2:31]3)=[CH:26][CH:25]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:1][C:2]1[C:3](=[O:21])[N:4]([C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:14])[C:5](=[O:12])[N:6]([CH2:8][CH2:9][CH2:10][N:32]2[CH2:33][C@H:34]3[C@:30]([C:27]4[CH:26]=[CH:25][C:24]([C:23]([F:22])([F:37])[F:36])=[CH:29][CH:28]=4)([CH2:35]3)[CH2:31]2)[N:7]=1

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 86645644HCID 86645644, compound

Product 1

HCID 59496099HCID 59496099, compoundYield 57.1%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 111,2-DichloroethaneSolvent

Procedure

3-[6-methyl-3,5-dioxo-4-(phenylcarbonyl)-4,5-dihydro-1,2,4-triazin-2(3H)-yl]propanal, Titanium (IV) isopropoxide (0.110 mL, 0.376 mmol) and (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (for reference preparation procedure see WO2005/080382, 62.6 mg, 0.276 mmol) were dissolved in 1,2-Dichloroethane (DCE) (9 mL) and the mixture was stirred at room temperature for 20 minutes. Afterwards the solution was cooled down to 0° C. and NaBH(AcO)3 (80 mg, 0.376 mmol) was added. The mixture was stirred at rt overnight. The day after it was quenched with water and diluted with DCM. The mixture was filtered and extracted; organic phase was washed with water and NaHCO3 saturated solution and solvent was eliminated under reduced pressure. Crude product was purified by flash chromatography (DCM to DCM/MeOH/NH3 9:1:0.1) affording the title compound 6-methyl-4-(phenylcarbonyl)-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (102 mg, 0.143 mmol, 57.1% yield). 6-methyl-2-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione formed during the reaction was recovered (25 mg, 0.063 mmol).

Workup

  1. temperatureAfterwards the solution was cooled down to 0° C.
  2. stirringThe mixture was stirred at rt overnight
  3. customThe day after it was quenched with water
  4. additiondiluted with DCM
  5. filtrationThe mixture was filtered
  6. extractionextracted
  7. washorganic phase was washed with water and NaHCO3 saturated solution and solvent
  8. customCrude product was purified by flash chromatography (DCM to DCM/MeOH/NH3 9:1:0.1)

Sources & evidence

ORD record
ord-bf98d489b6394821a6ad79cd54cd085c
Source dataset
uspto-grants-2012_07
Patent number
US08217168B2

Reaction notes

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