1,2-Dichloroethane → 4-(2-Fluorophenyl)-1-(4-{(1s,5r)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1h)-pyrimidinone hydrochloride

HRID 1514451노트

반응식

HRID 1514451 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][CH2:16][CH:17]=O)[C:10](=[O:19])[N:9]=1.[F:20][C:21]([F:35])([F:34])[C:22]1[CH:27]=[CH:26][C:25]([C@:28]23[CH2:33][C@H:32]2[CH2:31][NH:30][CH2:29]3)=[CH:24][CH:23]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:54]CCCl>>[ClH:54].[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][N:30]2[CH2:31][C@H:32]3[C@:28]([C:25]4[CH:24]=[CH:23][C:22]([C:21]([F:20])([F:35])[F:34])=[CH:27][CH:26]=4)([CH2:33]3)[CH2:29]2)[C:10](=[O:19])[N:9]=1

참가 물질

6

반응물 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 592428054-[4-(2-Fluoro-phenyl)-2-oxo-2H-pyrimidin-1-yl]-butyraldehydeHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

생성물 1

HCID 686995284-(2-Fluorophenyl)-1-(4-{(1s,5r)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1h)-pyrimidinone hydrochloride수율 58%

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온도
0 °C

실험 절차

4-[4-(2-Fluoro-phenyl)-2-oxo-2H-pyrimidin-1-yl]-butyraldehyde (Prep41, 50 mg, 0.19 mmol) was dissolved in DCE (5.5 ml). The resulting solution was cooled at 0° C. and then (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 53 mg, 0.23 mmol), AcOH (13 μl) and NaBH(AcO)3 (45 mg, 0.21 mmol) were added. The mixture was stirred for 10 minutes at 0° C. 1N NaOHaq was added and the product was extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The crude was purified by flash chromatography with DCM-MeOH—NH4OH (20-0.2-0.2) to give 52 mg of the title compound (58% yield) as a free base.

후처리

  1. addition1N NaOHaq was added
  2. extractionthe product was extracted with DCM
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated
  5. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (20-0.2-0.2)

출처 및 근거

ORD 기록
ord-9d8bbfb859294735a52ebe627231fddb
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08222266B2

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