Potassium Carbonate → 2-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehyde

HRID 1517560Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1517560
[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:24])([F:23])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][NH:17][CH:18]=1)[CH2:9][CH2:8]3.C(=O)([O-])[O-].[K+].[K+].Br[C:32]1[C:37]([CH:38]=[O:39])=[CH:36][CH:35]=[CH:34][N:33]=1.CN[C@@H]1CCCC[C@H]1NC>C(OCC)(=O)C.[Cu]I.C1(C)C=CC=CC=1>[Cl:1][C:2]1[S:6][C:5]2[C:7]3([O:20][CH2:21][C:22]([F:23])([F:24])[C:4]=2[CH:3]=1)[CH2:12][CH2:11][N:10]([CH2:13][C:14]1[C:15]([CH3:19])=[N:16][N:17]([C:32]2[C:37]([CH:38]=[O:39])=[CH:36][CH:35]=[CH:34][N:33]=2)[CH:18]=1)[CH2:9][CH2:8]3

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 47149512-BromonicotinaldehydeHCID 178434546HCID 178434546, Verbindung

Produkt 1

HCID 582685962-[4-[(2-Chloro-4,4-difluoro-spiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methyl-pyrazol-1-yl]pyridine-3-carbaldehydeAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a 250 mL flask are added copper(I) iodide (1.91 g, 10.03 mmol), 2-chloro-4,4-difluoro-1′-[(3-methyl-1H-pyrazol-4-yl)methyl]spiro[5H-thieno[2,3-c]pyran-7,4′-piperidine] (25 g, 66.87 mmol), potassium carbonate (19.60 g, 140.43 mmol), toluene (50 mL) and a stirring bar. The reaction mixture is degassed by 5 vacuum/refill cycles. Then, 2-bromo-3-formyl pyridine (18.66 g, 100.31 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (3.16 mL, 20.06 mmol) are added. The reaction is stirred at room temperature for 5 minutes. Then, it is immersed in a preheated oil bath at 115° C. and stirred for 15 h at that temperature. Reaction mixture is cooled to room temperature, diluted with 300 mL of ethyl acetate and filtered through celite. It is washed with ethyl acetate (100 mL) and aqueous solution of ammonium hydroxide (3%) (4×100 mL) to remove copper traces, and then, it is washed with water (50 mL) and brine (50 mL). Solution is dried over sodium sulfate. The solvent is evaporated in vacuo to give a tan solid. Solid was filtered through a pad of silica gel using as eluent 2-propanol/dichloromethane (3% to 5% of 2-propanol) to give the title compound in 69% yield. MS (m/z): 479 (M+1).

Aufarbeitung

  1. customThe reaction mixture is degassed by 5 vacuum/refill cycles
  2. customThen, it is immersed in a preheated oil bath at 115° C.
  3. stirringstirred for 15 h at that temperature
  4. customReaction mixture
  5. temperatureis cooled to room temperature
  6. filtrationfiltered through celite
  7. washIt is washed with ethyl acetate (100 mL) and aqueous solution of ammonium hydroxide (3%) (4×100 mL)
  8. customto remove copper traces
  9. washit is washed with water (50 mL) and brine (50 mL)
  10. dry with materialSolution is dried over sodium sulfate
  11. customThe solvent is evaporated in vacuo
  12. customto give a tan solid
  13. filtrationSolid was filtered through a pad of silica gel using as eluent 2-propanol/dichloromethane (3% to 5% of 2-propanol)

Quellen und Nachweise

ORD-Eintrag
ord-784521c1cba14596b23ed9bd4cb56911
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08232289B2

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