Hydrochloric Acid → 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide

HRID 2273932Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2273932
[N:1]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:15])([F:14])[F:13])[CH:5]=1)=[C:2]=[S:3].[CH3:16][NH:17][C:18](=[O:33])[C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]2([C:30]#N)[CH2:29][CH2:28][CH2:27]2)=[CH:21][C:20]=1[F:32].C[OH:35].Cl>CN(C=O)C.O>[CH3:16][NH:17][C:18](=[O:33])[C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:2](=[S:3])[N:1]([C:4]3[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([C:12]([F:13])([F:15])[F:14])[CH:5]=3)[C:30](=[O:35])[C:26]32[CH2:29][CH2:28][CH2:27]3)=[CH:21][C:20]=1[F:32]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 441395204-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide

Produkt 1

HCID 119577564-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamideAusbeute 57 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 4-isothiocyanato-2-trifluoromethylbenzonitrile (1a) (2.16 g, 9.47 mmol) and N-methyl-4-(1-cyanocyclobutylamino)-2-fluorobenzamide (52c) (1.303 g, 5.27 mmol) in DMF (20 ml) was heated under microwave irradiation at 80° C. for 16 hours. To this mixture was added methanol (50 ml) and aq. 2N HCl (20 ml). The second mixture was refluxed for 3 hours. After being cooled to room temperature, the reaction mixture was poured into cold water (100 ml) and extracted with ethyl acetate (150 ml). The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane:acetone, 95:5) to yield N-methyl-4-[7-(4-cyano-3-trifluoromethylphenyl)-8-oxo-6-thioxo-5,7-diaza-spiro[3.4]oct-5-yl]-2-fluorobenzamide (52d) [RD162] (1.43 g, 3.0 mmol, 57%), the structure of which is illustrated in Formula 28, as a yellow powder.

Aufarbeitung

  1. temperatureThe second mixture was refluxed for 3 hours
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (150 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customchromatographed (dichloromethane:acetone, 95:5)

Quellen und Nachweise

ORD-Eintrag
ord-69ce9ab72cf3468ba623e249cecc0e7f
Quelldatensatz
uspto-grants-2015_09
Patentnummer
US09126941B2

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