Cesium carbonate → 2-[5-Chloro-2-(2-methyl-5-phenyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methyl-benzamide

HRID 62484

Reaktionsgleichung

Reaktionsgleichung von HRID 62484
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl[C:48]1[CH:53]=[C:52]([NH:54][C:55]2[CH:64]=[CH:63][CH:62]=[CH:61][C:56]=2[C:57]([NH:59][CH3:60])=[O:58])[C:51]([Cl:65])=[CH:50][N:49]=1.[CH3:66][N:67]1[C:71]([NH2:72])=[CH:70][C:69]([C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)=[N:68]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:65][C:51]1[C:52]([NH:54][C:55]2[CH:64]=[CH:63][CH:62]=[CH:61][C:56]=2[C:57]([NH:59][CH3:60])=[O:58])=[CH:53][C:48]([NH:72][C:71]2[N:67]([CH3:66])[N:68]=[C:69]([C:73]3[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=3)[CH:70]=2)=[N:49][CH:50]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 5177791-Methyl-3-phenyl-1H-pyrazol-5-amineHCID 634876Binap, (A+-)-HCID 575168912-[(2,5-Dichloro-4-pyridinyl)amino]-N-methylbenzamide

Produkt 1

HCID 462166382-[5-Chloro-2-(2-methyl-5-phenyl-2H-pyrazol-3-ylamino)-pyridin-4-ylamino]-N-methyl-benzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A 50-mL sealed tube was charged with Pd(OAc)2 (18 mg, 0.08 mmol) and 2,2′-bis (diphenylphosphino)-1,1′-binaphthyl (BINAP, 50 mg, 0.08 mmol) in 1,4-dioxane (10 mL). The mixture was degassed using bubbling nitrogen for 40 min and heated at 50° C. for 1 h. Then the mixture was cooled to room temperature whereupon 2-[(2,5-dichloro-4-pyridinyl)amino]-N-methyl-benzamide (300 mg, 1.01 mmol), 2-methyl-5-phenyl-2H-pyrazol-3-ylamine (704 mg, 4.06 mmol) and cesium carbonate (960 mg, 2.96 mmol) were added under an inert atmosphere. The tube was sealed and heated at 120° C. overnight. The reaction mixture was concentrated under reduced pressure and the crude product was purified by column chromatography (silica gel, eluted with dichloromethane-methanol (DCM-MeOH) 99:1 followed by purification by preparatory TLC to afford the desired compound as a off white solid (25 mg, 5%). 1H NMR (400 MHz, DMSO-d6) δ 2.76 (d, 3H, J=4.52 Hz), 3.68 (s, 3H), 6.69 (s, 1H), 6.85 (s, 1H), 7.07-7.14 (m, 1H), 7.25-7.31 (m, 1H), 7.36-7.42 (m, 2H), 7.46-7.53 (m, 1H), 7.63 (d, 1H, J=8.08 Hz), 7.69 (d, 1H, J=7.4 Hz), 7.75 (d, 2H, J=7.16 Hz), 8.04 (s, 1H), 8.69 (brs, 1H), 8.81 (s, 1H), 10.13 (s, 1H). LC-MS calculated for C23H21ClN6O (M+H) 433.15, found 433.3. HPLC purity 96% at λ=200 nm and 99% at λ=260 nm.

Aufarbeitung

  1. customA 50-mL sealed tube
  2. customThe mixture was degassed
  3. customusing bubbling nitrogen for 40 min
  4. additionwere added under an inert atmosphere
  5. customThe tube was sealed
  6. temperatureheated at 120° C. overnight
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. customthe crude product was purified by column chromatography (silica gel
  9. washeluted with dichloromethane-methanol (DCM-MeOH) 99:1
  10. customfollowed by purification by preparatory TLC

Quellen und Nachweise

ORD-Eintrag
ord-25932ce56be542ae9b1ecb73bb32d2ab
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446034B2

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