Acetic Acid → 2,4-dioxo-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochloride

HRID 12765Notes

Reaction equation

HRID 12765 reaction equation
[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]1[CH2:11][CH2:12][CH2:13][CH:14]=O.[F:16][C:17]([F:31])([F:30])[C:18]1[CH:23]=[CH:22][C:21]([C@:24]23[CH2:29][C@H:28]2[CH2:27][NH:26][CH2:25]3)=[CH:20][CH:19]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:50]C(Cl)C>O>[ClH:50].[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]1[CH2:11][CH2:12][CH2:13][CH2:14][N:26]1[CH2:27][C@H:28]2[C@:24]([C:21]3[CH:20]=[CH:19][C:18]([C:17]([F:16])([F:31])[F:30])=[CH:23][CH:22]=3)([CH2:29]2)[CH2:25]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 589942302,4-Dioxo-1-(4-oxo-butyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrileHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 686937242,4-dioxo-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochlorideYield 53%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2,4-dioxo-1-(4-oxo-butyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (Prep55, 70 mg, 0.34 mmol) in dichloroethane (5 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 76 mg, 0.34 mmol) was added. The suspension was cooled at 0° C. and then AcOH (30 mg, 0.68 mmol) and NaBH(AcO)3 (79 mg, 0.38 mmol) were added and the mixture stirred at 0° C. for 4 hours. Water was added and the solvent was evaporated under vacuum, the residue re-dissolved in ethyl acetate and the mixture washed with aqueous saturated NaHCO3 solution. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1) to give the title compound as a white solid (86 mg, 53% yield) as free base

Workup

  1. customthe solvent was evaporated under vacuum
  2. dissolutionthe residue re-dissolved in ethyl acetate
  3. washthe mixture washed with aqueous saturated NaHCO3 solution
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1)

Sources & evidence

ORD record
ord-f6673334702b4bd89781c4b98bd8b4ab
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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