HOAt → 2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (6-bromo-pyridin-3-yl)-amide

HRID 557733

Reaktionsgleichung

Reaktionsgleichung von HRID 557733
[C:1]1([C:7]2[O:8][C:9]([C:15]([F:18])([F:17])[F:16])=[C:10]([C:12]([OH:14])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:19][C:20]1[N:25]=[CH:24][C:23]([NH2:26])=[CH:22][CH:21]=1.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[Br:19][C:20]1[N:25]=[CH:24][C:23]([NH:26][C:12]([C:10]2[N:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][C:9]=2[C:15]([F:18])([F:17])[F:16])=[O:14])=[CH:22][CH:21]=1

Komponenten

6

Edukt 4

HCID 181649HOAtHCID 6428116-Bromopyridin-3-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27764382-Phenyl-5-(trifluoromethyl)-oxazole-4-carboxylic acid

Produkt 1

HCID 576521452-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (6-bromo-pyridin-3-yl)-amideAusbeute 83,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (3.0 g, 11.7 mmol), 6-bromo-pyridin-3-ylamine (2.0 g, 11.7 mmol), 1-hydroxy-7-azabenzotriazole (HOAT) (2.4 g, 17.5 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.4 g, 17.5 mmol) in anhydrous dichloromethane (100 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried and concentrated to give a solid. Recrystallization of the crude solid from ethyl acetate/hexane/methanol gave 4.04 g of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (6-bromo-pyridin-3-yl)-amide. The mother liquor was purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane) to give an additional 200 mg of 2-phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid (6-bromo-pyridin-3-yl)-amide (4.24 g in total, 88%) as a light brown solid. LCMS calcd for C16H9BrF3N3O2 (m/e) 412, obsd 413 (M+H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated
  6. customto give a solid
  7. customRecrystallization of the crude solid from ethyl acetate/hexane/methanol

Quellen und Nachweise

ORD-Eintrag
ord-740a49f053324e32a9e86c3c2888aa5c
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08058299B2

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