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

反応式

HRID 240819 の反応式
[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]

参加物

7

反応物 4

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

生成物 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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-c982c58467e6497a88a329d72b4a5d5b
出典データセット
uspto-grants-2014_02
特許番号
US08648105B2

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