Oxalyl chloride → N-(4-benzoylpyrrolidino)-1-(4-methoxyphenyl)-3-(methylthio)-1H-pyrazole-5-carboxamide

HRID 2186224Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2186224
[C:1](Cl)(=O)[C:2](Cl)=O.[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:19]([C:20]([OH:22])=O)=[CH:18][C:17]([S:23][CH3:24])=[N:16]2)=[CH:11][CH:10]=1.N[C:26]1[CH:38]=[CH:37][C:29]([C:30](N2CCCC2)=[O:31])=[CH:28][CH:27]=1>CN(C=O)C.C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:30]([CH:2]1[CH2:1][N:15]([NH:16][C:20]([C:19]2[N:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH3:7])=[CH:14][CH:13]=3)[N:16]=[C:17]([S:23][CH3:24])[CH:18]=2)=[O:22])[CH2:12][CH2:11]1)(=[O:31])[C:29]1[CH:28]=[CH:27][CH:26]=[CH:38][CH:37]=1

Komponenten

7

Edukt 3

HCID 65578Oxalyl chlorideHCID 5778004-(Pyrrolidin-1-ylcarbonyl)anilineHCID 181773011-(4-Methoxyphenyl)-3-methylthio-1H-pyrazole-5-carboxylic acid

Produkt 1

HCID 10238249N-(4-benzoylpyrrolidino)-1-(4-methoxyphenyl)-3-(methylthio)-1H-pyrazole-5-carboxamideAusbeute 212,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

Oxalyl chloride (140 μl, 1.6 mmol) and dry DMF (2 drops) were added at room temperature to 1-(4-methoxyphenyl)-3-methylthio-1H-pyrazole-5-carboxylic acid (275 mg, 1.0 mmol) in dry CH2Cl2 (8 mL) and stirred for 100 minutes under N2. The resulting solution was evaporated and placed briefly under high vacuum before redissolving in CH2Cl2 (8 mL). (4-aminobenzoyl)pyrrolidine (198 mg, 1.0 mmol) was added, followed by 4-dimethylaminopyridine (190 mg, 1.6 mmol). The resulting mixture was stirred at room temperature for 17 hours, diluted with CH2Cl2, and extracted with H2O. The aqueous extract was extracted with CH2Cl2, the combined organic extracts were extracted with brine. The organic layer was dried over Na2SO4, filtered, and evaporated. The crude product was chromatographed on silica gel (75-100% EtOAc/hexanes) to yield the desired product (464 mg, 100%). 1H NMR (CDCl3): δ7.91 (bs, 1H), 7.44 (s, 4H), 7.39 (d, 2H, J=8.8), 6.97 (d, 2H, J=8.8), 6.83 (s, 1H), 3.84 (s, 3H), 3.62 (t, 2H, J=6.6), 3.42 (t, 2H, J=6.6), 2.57 (s, 3H), 1.91 (m, 4H).

Aufarbeitung

  1. customThe resulting solution was evaporated
  2. dissolutionbefore redissolving in CH2Cl2 (8 mL)
  3. stirringThe resulting mixture was stirred at room temperature for 17 hours
  4. extractionextracted with H2O
  5. extractionThe aqueous extract
  6. extractionwas extracted with CH2Cl2
  7. extractionthe combined organic extracts were extracted with brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was chromatographed on silica gel (75-100% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-7e81a3a0b6db41e3bd91e6ce15d00d5c
Quelldatensatz
uspto-grants-2002_06
Patentnummer
US06403620B1

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