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

반응식

HRID 240819 반응식
[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]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 66721954N,N-Dimethyl 4-[4-(1-cyanocyclobutylamino)phenyl]butanamide2회

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-c982c58467e6497a88a329d72b4a5d5b
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648105B2

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