Cesium carbonate → 7-[8-(2-Methoxy-phenyl)[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester

HRID 1890039Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1890039
Cl[C:2]1[N:18]=[C:5]2[C:6]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[O:16][CH3:17])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[C:19]([O:23][C:24]([N:26]1[CH2:32][CH2:31][C:30]2[CH:33]=[CH:34][C:35]([NH2:37])=[CH:36][C:29]=2[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C1(P(C2CCCCC2)C2(P(C3CCCCC3)C3CCCCC3)CC=CC=C2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[C:19]([O:23][C:24]([N:26]1[CH2:32][CH2:31][C:30]2[CH:33]=[CH:34][C:35]([NH:37][C:2]3[N:18]=[C:5]4[C:6]([C:10]5[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=5[O:16][CH3:17])=[CH:7][CH:8]=[CH:9][N:4]4[N:3]=3)=[CH:36][C:29]=2[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 11402789Tert-butyl 7-amino-4,5-dihydro-1H-benzo[D]azepine-3(2H)-carboxylateHCID 674814532-Chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridineHCID 866483582,2-Bis-dicyclohexylphosphanyl-biphenyl

Produkt 1

HCID 596124757-[8-(2-Methoxy-phenyl)[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl esterAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A Schlenck flask was charged with palladium acetate (0.0966 g, 0.430 mmol), triphenylphosphine (0.4513 g, 1.721 mmol), and 1,4-dioxane (6 mL) and the mixture was stirred for 5 min until it turned bright yellow. 8-Bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (0.500 g, 2.15 mmol), 2-methoxybenzeneboronic acid (0.490 g, 3.23 mmol), N,N-dimethylformamide (10.00 mL), and 1.00 N sodium carbonate in water (4.3 mL, 4.3 mmol) were added successively and the reaction was heated at 80° C. overnight, cooled to room temperature, diluted with dichloromethane, filtered through diatomaceous earth and concentrated. The reaction was purified via chromatography (silica gel 10%→20% ethyl acetate in hexanes) and concentrated to give 2-chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.464 g, 83%). MS=260 (MH)+. 311b) To an oven-dried Schlenck flask under an atmosphere of argon was added 2-chloro-8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.460 g, 1.77 mmol), 7-amino-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.558 g, 2.12 mmol), palladium acetate (0.0875 g, 0.390 mmol), 2,2-bis-dicyclohexylphosphanyl-biphenyl (0.242 g, 0.443 mmol), cesium carbonate (1.44 g, 4.43 mmol), followed by 1,4-dioxane (12.00 mL) and was degassed under an atmosphere of argon for 5 min and heated at 100° C. overnight, cooled at room temperature, diluted with dichloromethane, filtered through diatomaceous earth and concentrated. The reaction was purified via chromatography (silica gel 20%-30% ethyl acetate/hexanes) and concentrated to give 7-[8-(2-methoxy-phenyl)[1,2,4]triazolo[1,5-a]pyridin-2-ylamino]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylic acid tert-butyl ester (0.744 g, 87%). 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.54 (s, 1H), 8.78 (d, 1H), 7.55 (m, 2H), 7.45 (m, 2H), 7.35 (s, 1H) 7.15 (m, 1H), 7.05 (m, 3H), 3.74 (s, 3H), 3.48 (m, 4H), 2.78 (m, 4H), 1.41 (s, 9H): MS=486 (MH)+.

Aufarbeitung

  1. customwas degassed under an atmosphere of argon for 5 min
  2. temperaturecooled at room temperature
  3. additiondiluted with dichloromethane
  4. filtrationfiltered through diatomaceous earth
  5. concentrationconcentrated
  6. customThe reaction was purified via chromatography (silica gel 20%-30% ethyl acetate/hexanes)
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-15fdab3a599e4ca2adb42c2b858e828b
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08501936B2

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