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

HRID 12808Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 12808
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH:16]=O)[CH:13]=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.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+].[Cl:52]C(Cl)C>CC(O)=O>[ClH:52].[ClH:52].[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:19])[NH:10][C:11](=[O:18])[N:12]([CH2:14][CH2:15][CH2:16][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)[CH:13]=1

Komponenten

7

Edukt 5

HCID 63651,1-DichloroethaneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 58994157HCID 58994157, VerbindungHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

Produkt 1

HCID 686919985-(4-methyl-3-pyridinyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione dihydrochlorideAusbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 3-[5-(4-Methyl-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep113, 84 mg, 0.32 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 74 mg, 0.32 mmol), and AcOH (23 μl) in dichloroethane (4 ml) was cooled to 0° C. NaBH(AcO)3 (72 mg, 0.34 mmol) was added portionwise. The mixture was stirred at 0° C. for 2 hours and at room temperature for 30 minutes and then basified with 1N NaOH. The product was extracted with DCM, the organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred for 5 hours in presence of PS-isocyanate. The mixture was filtered and the solvent was evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98:2:0.2) to give 41 mg of the free base of title compound (27% yield).

Aufarbeitung

  1. extractionThe product was extracted with DCM
  2. dry with materialthe organic phase was dried (Na2SO4)
  3. customevaporated
  4. dissolutionThe residue was redissolved in DCM
  5. stirringstirred for 5 hours in presence of PS-isocyanate
  6. filtrationThe mixture was filtered
  7. customthe solvent was evaporated
  8. customThe crude was purified by flash chromatography
  9. washeluting with DCM-MeOH—NH4OH (98:2:0.2)

Quellen und Nachweise

ORD-Eintrag
ord-2e06fa0ac03542c299b6b396a177ad76
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727988B2

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