Dicyclohexylphosphine → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)acetamide

HRID 1036301

Reaktionsgleichung

Reaktionsgleichung von HRID 1036301
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][C:19]3[CH:20]=[N:21][C:22](Cl)=[C:23]([CH3:25])[CH:24]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[F:28][C:29]([F:40])([F:39])[C:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[CH:32][N:31]=1.C1(PC2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][C:19]3[CH:24]=[C:23]([CH3:25])[C:22]([C:34]4[CH:33]=[CH:32][N:31]=[C:30]([C:29]([F:40])([F:39])[F:28])[CH:35]=4)=[N:21][CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 13239DicyclohexylphosphineHCID 62657Potassium Phosphate, TribasicHCID 451588802-(Trifluoromethyl)pyridine-4-boronic acidHCID 58447745N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-methylpyridin-3-yl)acetamide

Produkt 1

HCID 46927436N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-2'-(trifluoromethyl)-2,4'-bipyridin-5-yl)acetamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a sealed tube were added N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(6-chloro-5-methylpyridin-3-yl)acetamide 148-1 (123 mg, 0.32 mmol), 2-(trifluoromethyl)pyridin-4-ylboronic acid (61 mg, 0.32 mmol), Pd(OAc)2 (3.6 mg, 0.016 mmol), 2,6-Dimethoxy-1,1′-biphenyl-2-yl)dicyclohexylphosphine (13.0 mg, 0.032 mmol) and K3PO4 (202 mg, 0.95 mmol). The tube and its contents were then purged with nitrogen. After degassed toluene (1.0 mL) was added, the mixture was stirred at 120° C. overnight. After cooling to room temperature, the mixture was poured into water and extracted with ethyl acetate (8 mL×3). The combined organic phases were dried over Na2SO4, and concentrated. The residue was purified by reverse phase HPLC to give to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-methyl-2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)acetamide 222. MS m/z 498.8 (M+1); 1H NMR 400 MHz (CDCl3) δ8.81 (d, 1H), 8.51 (d, 1H), 8.35 (s, 1H), 8.11 (d, 1H), 7.91 (s, 1H), 7.89 (s, 1H), 7.68-7.64 (m, 2H), 7.30 (dd, 1H), 3.80-3.75 (m, 4H), 3.63 (t, 2H), 3.14 (t, 2H), 3.11 (t, 2H), 2.39 (s, 3H), 2.14 (s, 3H).

Aufarbeitung

  1. customThe tube and its contents were then purged with nitrogen
  2. customAfter degassed toluene (1.0 mL)
  3. additionwas added
  4. temperatureAfter cooling to room temperature
  5. additionthe mixture was poured into water
  6. extractionextracted with ethyl acetate (8 mL×3)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC
  10. customto give

Quellen und Nachweise

ORD-Eintrag
ord-4b679c6cf73242689f1ed7722178b942
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08546396B2

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