Sodium triacetoxyborohydride → 6-bromo-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione

HRID 1513337Notes

Reaction equation

HRID 1513337 reaction equation
[Br:1][C:2]1[C:3](=[O:21])[N:4](C(C2C=CC=CC=2)=O)[C:5](=[O:12])[N:6]([CH2:8][CH2:9][CH:10]=O)[N:7]=1.[CH3:22][C:23]12[CH2:28][C:27]1([C:29]1[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=1)[CH2:26][NH:25][CH2:24]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([N])(=O)C1C=CC=CC=1>ClCCCl>[Br:1][C:2]1[C:3](=[O:21])[NH:4][C:5](=[O:12])[N:6]([CH2:8][CH2:9][CH2:10][N:25]2[CH2:26][C:27]3([C:29]4[CH:30]=[CH:31][C:32]([C:35]([F:36])([F:38])[F:37])=[CH:33][CH:34]=4)[C:23]([CH3:22])([CH2:28]3)[CH2:24]2)[N:7]=1

Participants

6

Reactant 4

HCID 5049666Sodium triacetoxyborohydrideHCID 534225311-Methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 594961013-[6-bromo-3,5-dioxo-4-(phenylcarbonyl)-4,5-dihydro-1,2,4-triazin-2(3H)-yl]propanalHCID 177534044CID 177534044

Product 1

HCID 686531246-bromo-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dioneYield 17.73%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

3-[6-bromo-3,5-dioxo-4-(phenylcarbonyl)-4,5-dihydro-1,2,4-triazin-2(3H)-yl]propanal (P7, 201 mg, 0.572 mmol) was dissolved in dry 1,2-Dichloroethane (DCE) (1.144 mL), then 1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (P15, Enantiomer 2, 138 mg, 0.572 mmol) was added and the mixture was stirred at room temperature for 10 minutes. The mixture was then cooled to 0° C. and left stirring at that temperature for 15 minutes. Afterwards, sodiumtriacetoxy borohydride (133 mg, 0.629 mmol) was added and the mixture was stirred at 0° C. for 2 hours. In situ cleavage of the benzoyl nitrogen protecting group was observed. It was then quenched with NH4Cl saturated solution and extracted with DCM. Organic phase was dried and concentrated under reduced pressure affording a crude as a yellow oil. The latter was purified by flash chromatography (SiO2, eluent: DCM to DCM/MeOH 95:5) affording 6-bromo-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (Enantiomer 2, 48 mg, 0.101 mmol, 17.73% yield) as a white powder.

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. waitleft
  3. stirringstirring at that temperature for 15 minutes
  4. stirringthe mixture was stirred at 0° C. for 2 hours
  5. customIt was then quenched with NH4Cl saturated solution
  6. extractionextracted with DCM
  7. customOrganic phase was dried
  8. concentrationconcentrated under reduced pressure
  9. customaffording a crude as a yellow oil
  10. customThe latter was purified by flash chromatography (SiO2, eluent: DCM to DCM/MeOH 95:5)

Sources & evidence

ORD record
ord-6c360085b7034f56bdd4bc3706d4a61a
Source dataset
uspto-grants-2012_07
Patent number
US08217168B2

Reaction notes

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