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

HRID 12765Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 12765
[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]1[CH2:11][CH2:12][CH2:13][CH:14]=O.[F:16][C:17]([F:31])([F:30])[C:18]1[CH:23]=[CH:22][C:21]([C@:24]23[CH2:29][C@H:28]2[CH2:27][NH:26][CH2:25]3)=[CH:20][CH:19]=1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[Cl:50]C(Cl)C>O>[ClH:50].[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]([C:9]#[N:10])=[CH:4][N:3]1[CH2:11][CH2:12][CH2:13][CH2:14][N:26]1[CH2:27][C@H:28]2[C@:24]([C:21]3[CH:20]=[CH:19][C:18]([C:17]([F:16])([F:31])[F:30])=[CH:23][CH:22]=3)([CH2:29]2)[CH2:25]1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 5049666Sodium triacetoxyborohydrideHCID 589942302,4-Dioxo-1-(4-oxo-butyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrileHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Produkt 1

HCID 686937242,4-dioxo-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-1,2,3,4-tetrahydro-5-pyrimidinecarbonitrile hydrochlorideAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 2,4-dioxo-1-(4-oxo-butyl)-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (Prep55, 70 mg, 0.34 mmol) in dichloroethane (5 mL), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 76 mg, 0.34 mmol) was added. The suspension was cooled at 0° C. and then AcOH (30 mg, 0.68 mmol) and NaBH(AcO)3 (79 mg, 0.38 mmol) were added and the mixture stirred at 0° C. for 4 hours. Water was added and the solvent was evaporated under vacuum, the residue re-dissolved in ethyl acetate and the mixture washed with aqueous saturated NaHCO3 solution. 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 as a white solid (86 mg, 53% yield) as free base

Aufarbeitung

  1. customthe solvent was evaporated under vacuum
  2. dissolutionthe residue re-dissolved in ethyl acetate
  3. washthe mixture washed with aqueous saturated NaHCO3 solution
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customThe crude was purified by flash chromatography with DCM-MeOH—NH4OH (97-3-1)

Quellen und Nachweise

ORD-Eintrag
ord-f6673334702b4bd89781c4b98bd8b4ab
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727988B2

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