Dimethylcarbamoyl Chloride → 3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-N,N-dimethyl-1-azetidinecarboxamide

HRID 525225

Reaktionsgleichung

Reaktionsgleichung von HRID 525225
[NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:27]=[C:26]5[C:21]([CH:22]=[CH:23][CH:24]=[N:25]5)=[CH:20][CH:19]=4)=[CH:14][C:13]=3[F:28])[C:8](=[O:11])[NH:9][N:10]=2)[CH2:2]1.C(N(CC)C(C)C)(C)C.[CH3:38][N:39]1[CH2:43]CC[C:40]1=[O:44].CN(C)C(Cl)=O>ClCCl>[F:28][C:13]1[CH:14]=[C:15]([C:18]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][CH:24]=[N:25]3)=[CH:20][CH:19]=2)[CH:16]=[CH:17][C:12]=1[N:7]1[C:8](=[O:11])[NH:9][N:10]=[C:6]1[CH2:5][CH:3]1[CH2:4][N:1]([C:40]([N:39]([CH3:43])[CH3:38])=[O:44])[CH2:2]1

Komponenten

6

Edukt 4

HCID 6598Dimethylcarbamoyl ChlorideHCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 673759915-(3-azetidinylmethyl)-4-[2-fluoro-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Produkt 1

HCID 673771443-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-N,N-dimethyl-1-azetidinecarboxamideAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a round bottom flask under nitrogen at room temperature, a mixture of 5-(3-azetidinylmethyl)-4-[2-fluoro-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (0.38 mmol) in dichloromethane (2 mL) was treated with N,N-diisopropylethylamine (0.77 mmol) by syringe and stirred for 2 min. The starting material did not dissolve. N-methyl-2-pyrrolidone (2 mL) was added to the mixture and some material dissolved. The mixture was heated with a heat gun to accelerate dissolution and was then left to cool to room temperature. Dimethylcarbamoyl chloride (0.38 mmol) was then added dropwise by syringe to the reaction, which was stirred for 1 h. The reaction mixture was concentrated to remove the dichloromethane. The resultant solution was directly purified by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH) and subsequently purified by silica gel chromatography (0-3% methanol/ethyl acetate) to provide the title compound as a white solid (31 mg, 18%). MS(ES)+ m/e 447.2 [M+H]+.

Aufarbeitung

  1. dissolutionThe starting material did not dissolve
  2. dissolutionsome material dissolved
  3. temperatureThe mixture was heated with a heat gun
  4. dissolutiondissolution
  5. waitwas then left
  6. stirringwas stirred for 1 h
  7. concentrationThe reaction mixture was concentrated
  8. customto remove the dichloromethane
  9. customThe resultant solution was directly purified by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH)
  10. customsubsequently purified by silica gel chromatography (0-3% methanol/ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-d2753fda6a104f389f33b7420d50a41a
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340529B2

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