Toluene → (S)-4-(3-methylpiperazin-1-yl)-1-(4-(trifluoromethyl)phenyl)pyrido[3,4-d]pyridazine

HRID 1514384Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1514384
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][C@@H:10]([CH3:14])[CH2:9]2)=[C:4]2[CH:15]=[N:16][CH:17]=[CH:18][C:3]=12.[F:19][C:20]([F:31])([F:30])[C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>C(OCC)(=O)C.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>[CH3:14][C@@H:10]1[NH:11][CH2:12][CH2:13][N:8]([C:5]2[N:6]=[N:7][C:2]([C:24]3[CH:25]=[CH:26][C:21]([C:20]([F:31])([F:30])[F:19])=[CH:22][CH:23]=3)=[C:3]3[CH:18]=[CH:17][N:16]=[CH:15][C:4]=23)[CH2:9]1

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 57657608(S)-1-chloro-4-(3-methylpiperazin-1-yl)pyrido[3,4-d]pyridazine

Produkt 1

HCID 57657602(S)-4-(3-methylpiperazin-1-yl)-1-(4-(trifluoromethyl)phenyl)pyrido[3,4-d]pyridazineAusbeute 70,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a round bottomed flask was added (S)-1-chloro-4-(3-methylpiperazin-1-yl)pyrido[3,4-d]pyridazine 4 (155 mg, 588 μmol), 4-trifluoromethylphenylboronic acid (167 mg, 882 μmol), tetrakis(triphenylphosphine)palladium (34 mg, 29 μmol), and 2 M aqueous sodium carbonate (588 μl, 1.18 mmol). Toluene (5.9 mL) was added and the reaction was heated to 100° C. After 16 h, the reaction was cooled to RT and diluted with ethyl acetate (70 mL). The organic layer was washed with 1×10 mL of sat. NaHCO3, 1×10 mL of brine. The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography (10:0.5:0.1) (CH2Cl2:MeOH:Et3N) afforded (S)-4-(3-methylpiperazin-1-yl)-1-(4-(trifluoromethyl)phenyl)pyrido[3,4-d]pyridazine 47 (154 mg, 70% yield). 1H-NMR (400 MHz, CDCl3): δ 9.55 (d, J=0.8 Hz, 1H), 8.90 (d, J=5.5 Hz, 1H), 7.86 (m, 4H), 7.73 (dd, J=5.5, 0.8 Hz, 1H), 4.09 (m, 2H), 3.37 (ddd, J=12.5, 11.0, 3.5 Hz, 1H), 2.23 (m, 3H), 2.99 (dd, J=12.5, 10.2 Hz, 1H), 2.85 (br s, 1H), 1.17 (d, J=6.3 Hz, 1H). MS 373.1 (calc'd) 374.0 (M+H, found).

Aufarbeitung

  1. temperaturethe reaction was cooled to RT
  2. washThe organic layer was washed with 1×10 mL of sat. NaHCO3, 1×10 mL of brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by column chromatography (10:0.5:0.1) (CH2Cl2:MeOH:Et3N)

Quellen und Nachweise

ORD-Eintrag
ord-da365d3bcaa144d49d1e974eb0f092b9
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222251B2

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