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

HRID 12758Notes

Reaction equation

HRID 12758 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[C:4](=[O:15])[NH:5][C:6](=[O:14])[N:7]([CH2:9][CH2:10][CH2:11][CH:12]=O)[CH:8]=1.[F:18][C:19]([F:33])([F:32])[C:20]1[CH:25]=[CH:24][C:23]([C@:26]23[CH2:31][C@H:30]2[CH2:29][NH:28][CH2:27]3)=[CH:22][CH:21]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:52]C(Cl)C>C(OCC)(=O)C>[ClH:52].[F:1][C:2]([F:17])([F:16])[C:3]1[C:4](=[O:15])[NH:5][C:6](=[O:14])[N:7]([CH2:9][CH2:10][CH2:11][CH2:12][N:28]2[CH2:29][C@H:30]3[C@:26]([C:23]4[CH:22]=[CH:21][C:20]([C:19]([F:18])([F:33])[F:32])=[CH:25][CH:24]=4)([CH2:31]3)[CH2:27]2)[CH:8]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 589941974-(5-Trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-butyraldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Product 1

HCID 866159525-(trifluoromethyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2,4(1H,3H)-pyrimidinedione hydrochlorideYield 76%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-butyraldehyde (Prep24, 22 mg, 0.09 mmol) in dichloroethane (1 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 204 mg, 0.09 mmol), AcOH (7.9 mg, 0.13 mmol) and NaBH(AcO)3 (22 mg, 0.18) were added and the mixture was stirred at room temperature overnight. Ethyl acetate was added and the solution was washed with aqueous saturated NaHCO3. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-1) to give the title compound (31 mg, 76% yield) as a free base.

Workup

  1. washthe solution was washed with aqueous saturated NaHCO3
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. customevaporated
  4. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-1)

Sources & evidence

ORD record
ord-21ed03dc71274ef3b0a08a758c9b90cc
Source dataset
uspto-grants-2010_06
Patent number
US07727988B2

Reaction notes

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