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

HRID 12764Notes

Reaction equation

HRID 12764 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][CH:13]=O.[F:15][C:16]([F:30])([F:29])[C:17]1[CH:22]=[CH:21][C:20]([C@:23]23[CH2:28][C@H:27]2[CH2:26][NH:25][CH2:24]3)=[CH:19][CH:18]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:49]C(Cl)C>>[ClH:49].[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][N:25]1[CH2:26][C@H:27]2[C@:23]([C:20]3[CH:19]=[CH:18][C:17]([C:16]([F:15])([F:30])[F:29])=[CH:22][CH:21]=3)([CH2:28]2)[CH2:24]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 589942042,4-Dioxo-1-(3-oxo-propyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrileHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 686933782,4-dioxo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochlorideYield 38%

Procedure

To a solution of 2,4-dioxo-1-(3-oxo-propyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (Prep35, 90 mg, 0.47 mmol) in dichloroethane (8 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 106 mg, 0.47 mmol), AcOH (42 mg, 0.7 mmol) and NaBH(AcO)3 (198 mg, 0.94 mmol) were added and the mixture was stirred at room temperature overnight. The solvent was evaporated under vacuum, the residue redissolved in ethyl acetate and the obtained 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 free base of the title compound as a white solid (70 mg, 38% yield).

Workup

  1. customThe solvent was evaporated under vacuum
  2. dissolutionthe residue redissolved in ethyl acetate
  3. washthe obtained 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-a14a8617c08141e78bf3ffd25e5ba2bd
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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