Hydrochloric Acid → 4-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3,4]octan-5-yl)phenyl)-N,N-dimethylbutanamide

HRID 240819

Reaktionsgleichung

Reaktionsgleichung von HRID 240819
[CH3:1][N:2]([CH3:21])[C:3](=[O:20])[CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]2([C:18]#N)[CH2:17][CH2:16][CH2:15]2)=[CH:9][CH:8]=1.[N:22]([C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([C:33]([F:36])([F:35])[F:34])[CH:26]=1)=[C:23]=[S:24].C[OH:38].Cl>CN(C=O)C.O>[C:29]([C:28]1[CH:31]=[CH:32][C:25]([N:22]2[C:18](=[O:38])[C:14]3([CH2:17][CH2:16][CH2:15]3)[N:13]([C:10]3[CH:11]=[CH:12][C:7]([CH2:6][CH2:5][CH2:4][C:3]([N:2]([CH3:21])[CH3:1])=[O:20])=[CH:8][CH:9]=3)[C:23]2=[S:24])=[CH:26][C:27]=1[C:33]([F:34])([F:36])[F:35])#[N:30]

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 66721954N,N-Dimethyl 4-[4-(1-cyanocyclobutylamino)phenyl]butanamide2×

Produkt 1

HCID 159516264-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3,4]octan-5-yl)phenyl)-N,N-dimethylbutanamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A mixture of N,N-Dimethyl 4-[4-(1-cyanocyclobutylamino)phenyl]butanamide (Formula 48) (58 mg, 0.20 mmol) and 4-isothiocyanato-2-trifluoromethyl benzonitrile (74 mg, 0.32 mmol) in DMF (3 mL) was heated under reflux for 2 hours. To this mixture was added methanol (20 mL) and aq. 1 N HCl (5 mL). The second mixture was refluxed for 1.5 h. After being cooled to room temperature, the reaction mixture was poured into cold water (50 mL) and extracted with ethyl acetate (50 mL). The organic layer was dried over MgSO4, concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 95:5) to give 4-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)phenyl)-N,N-dimethylbutanamide, NC56 (Formula 49) (44 mg, 42%) as a pale yellowish solid. 1H NMR δ 7.98 (s, 1H), 7.97 (d, 1H, J=8.2 Hz), 7.86 (d, 1H, J=8.2 Hz), 7.42 (d, 2H, J=8.3 Hz), 7.22 (d, 2H, J=8.3 Hz), 2.99 (s, 3H), 2.96 (s, 3H), 2.78 (t, 2H, J=7.5 Hz), 2.62-2.70 (m, 2H), 2.52-2.63 (m, 2H), 2.40 (t, 2H, J=7.5 Hz), 2.15-2.30 (m, 1H), 2.04 (p, 2H, J=7.5 Hz), 1.62-1.73 (m, 1H).

Aufarbeitung

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. temperatureThe second mixture was refluxed for 1.5 h
  4. extractionextracted with ethyl acetate (50 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 95:5)

Quellen und Nachweise

ORD-Eintrag
ord-c982c58467e6497a88a329d72b4a5d5b
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08648105B2

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