Potassium Fluoride → 5-(5-chloro-2-fluoro-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 12793

Reaktionsgleichung

Reaktionsgleichung von HRID 12793
I[C:2]1[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]2[CH2:16][C@H:15]3[C@:13]([C:17]4[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=4)([CH2:14]3)[CH2:12]2)[CH:7]=1.[F:29][C:30]1[C:35](B(O)O)=[CH:34][C:33]([Cl:39])=[CH:32][N:31]=1.[F-].[K+]>CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[ClH:39].[ClH:39].[Cl:39][C:33]1[CH:34]=[C:35]([C:2]2[C:3](=[O:28])[NH:4][C:5](=[O:27])[N:6]([CH2:8][CH2:9][CH2:10][N:11]3[CH2:16][C@H:15]4[C@:13]([C:17]5[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=5)([CH2:14]4)[CH2:12]3)[CH:7]=2)[C:30]([F:29])=[N:31][CH:32]=1

Komponenten

6

Edukt 3

HCID 522689Potassium FluorideHCID 249017795-Chloro-2-fluoropyridine-3-boronic AcidHCID 675197195-iodo-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

Produkt 1

HCID 866159605-(5-chloro-2-fluoro-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 6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 5-iodo-1-{3-[(1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hex-3-yl]-propyl}-1H-pyrimidine-2,4-dione (Prep 40, 150 mg, 0.3 mmol), 2-fluoro-5-chloropyridine-3-boronic acid (142 mg, 0.9 mmol), KF (157 mg, 2.7 mmol), and Pd(OAc)2 (20 mg) in degassed MeOH (4 ml) was placed in a microwave oven and warmed at 120° C. for 25 minutes. The mixture was filtered, MeOH was evaporated and the crude partitioned between brine and ethyl acetate. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with ethyl acetate-NH4OH (0.5%) to give the title compound (10 mg, 6% yield).

Aufarbeitung

  1. customwas placed in a microwave oven
  2. filtrationThe mixture was filtered
  3. customMeOH was evaporated
  4. customthe crude partitioned between brine and ethyl acetate
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customevaporated
  7. customthe crude was purified by flash chromatography with ethyl acetate-NH4OH (0.5%)

Quellen und Nachweise

ORD-Eintrag
ord-2f63d5a76ab14a41b250ef46922cb2d2
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727988B2

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