Pyridine → 2,6-dichloro-3-[[[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]-N-(1-methylethyl)-4-pyridinecarboxamide

HRID 227586Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 227586
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([OH:15])=O)=[CH:11][C:10]([C:16]([F:19])([F:18])[F:17])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[Cl:26][C:27]1[N:38]=[C:37]([Cl:39])[C:30]2[NH:31]C(=O)O[C:34](=[O:35])[C:29]=2[CH:28]=1.N1C=CC=CC=1.[CH:46]([NH2:49])([CH3:48])[CH3:47]>ClCCl.CN(C=O)C.C(#N)C>[Cl:39][C:37]1[C:30]([NH:31][C:13]([C:12]2[N:8]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[N:9]=[C:10]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)=[O:15])=[C:29]([C:34]([NH:49][CH:46]([CH3:48])[CH3:47])=[O:35])[CH:28]=[C:27]([Cl:26])[N:38]=1

Komponenten

9

Edukt 5

HCID 1049PyridineHCID 6363IsopropylamineHCID 65578Oxalyl chlorideHCID 113921841-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acidHCID 866076396,8-dichloro-2H-pyrido[3,4-d][1,3]oxazine-2,4(1H)-dione

Produkt 1

HCID 102082712,6-dichloro-3-[[[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]carbonyl]amino]-N-(1-methylethyl)-4-pyridinecarboxamideAusbeute 52,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To a solution of 268 mg (0.92 mmol) of 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (from Step F) in 5 mL of dichloromethane was added 160 μL (1.84 mmol) of oxalyl chloride and two drops of DMF in sequence at room temperature. The mixture was then stirred at the same temperature for 1 hour. The crude mixture was then concentrated in vacuo. The resulting mixture was dissolved with 5 mL of acetonitrile followed by additions of 280 mg (0.92 mmol) of the compound prepared in Step D and 298 μL (3.68 mmol) of pyridine in sequence. The reaction mixture was warmed to 70° C. for 2 hours and allowed to cool to room temperature. A solution of 157 μL (1.84 mmol) of isopropylamine in 1 mL of acetonitrile was added to the mixture and it was warmed to 60° C. for 1 hour. The reaction was allowed to cool to room temperature and quenched with water. The aqueous layer was extracted with ethyl acetate and the organic layer was dried with MgSO4 and concentrated in vacuo. The resulting mixture was purified with a silica gel column to give 250 mg of the title compound, a compound of the invention, as a white solid (52%). m.p. 240-242° C.

Aufarbeitung

  1. concentrationThe crude mixture was then concentrated in vacuo
  2. dissolutionThe resulting mixture was dissolved with 5 mL of acetonitrile
  3. temperatureto cool to room temperature
  4. temperaturewas warmed to 60° C. for 1 hour
  5. temperatureto cool to room temperature
  6. customquenched with water
  7. extractionThe aqueous layer was extracted with ethyl acetate
  8. dry with materialthe organic layer was dried with MgSO4
  9. concentrationconcentrated in vacuo
  10. customThe resulting mixture was purified with a silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-81af3bca5ec8412198645a2f62be8caa
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07560564B2

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