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 1514451Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1514451
[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

Komponenten

6

Edukt 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

Produkt 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 hydrochlorideAusbeute 58 %

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-9d8bbfb859294735a52ebe627231fddb
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222266B2

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