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

反応式

HRID 12756 の反応式
[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

参加物

7

反応物 5

HCID 111,2-Dichloroethane2 回HCID 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

生成物 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 hydrochloride収率 51%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-97bae88de57f4bc1aa41a5f634eb98c9
出典データセット
uspto-grants-2010_06
特許番号
US07727988B2

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