Triethylamine → 3-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4-(methylsulfonyl)thiophene-2-carboxamide

HRID 1686185Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1686185
Cl.[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH2:14])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1.C(N(CC)CC)C.[Cl:23][C:24]1[C:28]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][S:26][C:25]=1[C:33](Cl)=[O:34]>C(Cl)Cl.CC#N>[Cl:23][C:24]1[C:28]([S:29]([CH3:32])(=[O:30])=[O:31])=[CH:27][S:26][C:25]=1[C:33]([NH:14][C:12]1[CH:11]=[N:10][N:9]([CH2:8][C:7]2[C:3]([CH3:2])=[N:4][O:5][C:6]=2[CH3:15])[CH:13]=1)=[O:34]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 27357753-Chloro-4-(Methylsulfonyl)Thiophene-2-Carbonyl ChlorideHCID 574222641-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

Produkt 1

HCID 43413323-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4-(methylsulfonyl)thiophene-2-carboxamideAusbeute 45,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirring mixture of ((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (500 mg, 2 mmol) in DCM (20 mL), cooled to 0° C. via an ice water bath, was added triethylamine (600 mg, 6 mmol). The mixture was stirred until all solids were in solution (˜10 minutes). 3-Chloro-4-(methylsulfonyl)thiophene-2-carbonyl chloride (543 mg, 2.1 mmol), in 2 mL CH3CN, was added via syringe to the free amine at 0° C. The ice bath was removed and the mixture was stirred for 2 hours. The reaction was diluted with dichloromethane (100 mL) and the organic phase was washed with H2O (200 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The solid was triturated with ethyl acetate/hexanes (1/5) to afford 3-chloro-N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-4 (methylsulfonyl)thiophene-2-carboxamide (375 mg, 45%) as a white solid. 1H NMR (CDCl3, 400 MHz): 2.20 (s, 3H), 2.43 (s, 4H), 3.22 (s, 3H), 5.05 (s, 2H), 7.57 (s, 1H), 7.94 (s, 1H), 8.41 (s, 1H), 8.59 (bs, 1H). LC/MS; [M+H] 415.5. Melting point: 202-204° C.

Aufarbeitung

  1. customwere in solution (˜10 minutes)
  2. customThe ice bath was removed
  3. stirringthe mixture was stirred for 2 hours
  4. additionThe reaction was diluted with dichloromethane (100 mL)
  5. washthe organic phase was washed with H2O (200 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe solid was triturated with ethyl acetate/hexanes (1/5)

Quellen und Nachweise

ORD-Eintrag
ord-5370151a9f374c80a3f929be293fe02d
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08148544B2

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