1,3-Dimethyl-1H-pyrazol-5-amine → 2-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acid

HRID 1472532

Reaktionsgleichung

Reaktionsgleichung von HRID 1472532
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])[C:5]([Cl:18])=[CH:4][N:3]=1.[CH3:19][N:20]1[C:24]([NH2:25])=[CH:23][C:22]([CH3:26])=[N:21]1.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.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:18][C:5]1[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])=[CH:7][C:2]([NH:25][C:24]2[N:20]([CH3:19])[N:21]=[C:22]([CH3:26])[CH:23]=2)=[N:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 575168952-[(2,5-Dichloro-4-pyridinyl)amino]benzoic acid

Produkt 1

HCID 462147742-({5-Chloro-2-[(1,3-dimethyl-1H-pyrazol-5-yl)amino]-4-pyridinyl}amino)benzoic acidAusbeute 22,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A pressure tube was charged with 2-[(2,5-dichloro-4-pyridinyl)amino]benzoic acid (1.0 g, 3.53 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (0.589 g, 5.30 mmol), (±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene (0.330 g, 0.530 mmol), tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3, 0.162 g, 0.177 mmol) and sodium tert-butoxide (0.849 g, 8.83 mmol) in 1,4-dioxane (30 mL). The tube was degassed with N2 and sealed and the reaction mixture was heated in an oil bath at 120° C. for 18 hours. The reaction mixture was evaporated to dryness under high vacuum. The residue was taken back in water solution and the pH was adjusted to ˜4 to 5 using 6.0 N hydrochloride acid. The reaction was concentrated to dryness and the resulting solid was dissolved in MeOH and purified by reverse-phase HPLC to give the title compound as a solid (285 mg, 21% yield). MS: M(C17H16ClN5O2)=357.79, (M+H)+=358, 360.

Aufarbeitung

  1. customThe tube was degassed with N2
  2. customsealed
  3. customThe reaction mixture was evaporated to dryness under high vacuum
  4. concentrationThe reaction was concentrated to dryness
  5. dissolutionthe resulting solid was dissolved in MeOH
  6. custompurified by reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-629ae6c70ed74c26a4e60c3a47bbb256
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012479B2

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