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

HRID 12756

반응식

HRID 12756 반응식
[F:1][C:2]([F:16])([F:15])[C:3]1[C:4](=[O:14])[NH:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][CH:11]=O)[CH:8]=1.[F:17][C:18]([F:32])([F:31])[C:19]1[CH:24]=[CH:23][C:22]([C@:25]23[CH2:30][C@H:29]2[CH2:28][NH:27][CH2:26]3)=[CH:21][CH:20]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:51]CCCl>C(OCC)(=O)C>[ClH:51].[F:1][C:2]([F:16])([F:15])[C:3]1[C:4](=[O:14])[NH:5][C:6](=[O:13])[N:7]([CH2:9][CH2:10][CH2:11][N:27]2[CH2:28][C@H:29]3[C@:25]([C:22]4[CH:21]=[CH:20][C:19]([C:18]([F:17])([F:32])[F:31])=[CH:24][CH:23]=4)([CH2:30]3)[CH2:26]2)[CH:8]=1

참가 물질

7

반응물 5

HCID 111,2-Dichloroethane2회HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 589941853-(5-Trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 866159515-(trifluoromethyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione hydrochloride수율 51%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 3-(5-trifluoromethyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-propionaldehyde (Prep21, 0.05 g, 0.21 mmol) in DCE (1 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 0.08 g, 0.35 mmol) in DCE (1 mL), AcOH (20 μl, 0.36 mmol) and NaBH(AcO)3 (0.09 g, 0.42) were added and the mixture was stirred at room temperature overnight. Ethyl acetate was added and the solution washed with aqueous saturated NaHCO3. 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 (0.04 mg, 51% yield) as a free base.

후처리

  1. washthe solution 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 (97-3-1)

출처 및 근거

ORD 기록
ord-97bae88de57f4bc1aa41a5f634eb98c9
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727988B2

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