Sodium Carbonate → 5-(2-fluorophenyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedione

HRID 12767

Reaktionsgleichung

Reaktionsgleichung von HRID 12767
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[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[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

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 27343542-Fluorophenylboronic 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 247592355-(2-fluorophenyl)-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2,4(1H,3H)-pyrimidinedioneAusbeute 76,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

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 (Prep40, 80 mg, 0.16 mmol) was dissolved in degassed DME-water solution (5-1, 10 mL). 0.2-Fluorophenyl-boronic acid (33 mg, 0.23 mmol), Na2CO3 (34 mg, 0.32 mmol), 2-(dicyclohexylphosphino)biphenyl (14 mg, 0.04 mmol) and Pd(PPh3)4 (46 mg, 0.04 mmol) were added and the mixture stirred for 3 hours at 90° C. The solvents were evaporated under vacuum and the crude was redissolved in ethyl acetate, and washed with water. The organic phase was dried (Na2SO4) and evaporated; the crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2) followed by SCX cartridge washing with MeOH and eluting with MeOH/NH3 95:5 to give the title compound (58 mg, 76% yield) as free base.

Aufarbeitung

  1. customThe solvents were evaporated under vacuum
  2. dissolutionthe crude was redissolved in ethyl acetate
  3. washwashed with water
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. customevaporated
  6. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (98-2-0.2)
  7. washwashing with MeOH
  8. washeluting with MeOH/NH3 95:5

Quellen und Nachweise

ORD-Eintrag
ord-ac266ee00d08487fa94d205c650ffd5e
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727988B2

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