Potassium Carbonate → (R)-(4,4-difluoropiperidin-1-yl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

HRID 1514380Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1514380
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]1[N:9]=[N:10][C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=12.[F:24][C:25]1([F:43])[CH2:30][CH2:29][N:28]([C:31](OC2C=CC([N+]([O-])=O)=CC=2)=[O:32])[CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>>[F:24][C:25]1([F:43])[CH2:30][CH2:29][N:28]([C:31]([N:6]2[CH2:5][CH2:4][N:3]([C:8]3[N:9]=[N:10][C:11]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[C:12]4[CH:17]=[CH:16][N:15]=[CH:14][C:13]=34)[C@H:2]([CH3:1])[CH2:7]2)=[O:32])[CH2:27][CH2:26]1

Komponenten

4

Edukt 3

HCID 11430Potassium CarbonateHCID 57657605(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazineHCID 576576134-Nitrophenyl 4,4-difluoropiperidin-1-carboxylate

Produkt 1

HCID 25227133(R)-(4,4-difluoropiperidin-1-yl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a 10 mL round bottomed flask was added (R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine 16 (110 mg, 360 μmol), 4-nitrophenyl 4,4-difluoropiperidin-1-carboxylate (124 mg, 432 μmol), and potassium carbonate (100 mg, 720 μmol). The reaction was heated to 80° C. overnight. After cooling to room temperature, the solvent was removed under vacuum, and the residue was redissolved in ethyl acetate and washed with water (10 mL), followed by NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography afforded (R)-(4,4-difluoropiperidin-1-yl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone 42. MS 452.2 (calc'd) 453.3 (M+H, found).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed under vacuum
  3. dissolutionthe residue was redissolved in ethyl acetate
  4. washwashed with water (10 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-2782ffec105844eb803ff3779f70ae38
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222251B2

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