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 1927380노트

반응식

HRID 1927380 반응식
[CH3:1][NH:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2([C:16]#N)[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:6][C:5]=1[F:18].[N:20]([C:23]1[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([C:31]([F:34])([F:33])[F:32])[CH:24]=1)=[C:21]=[S:22].C[OH:36].Cl>CN(C=O)C.O>[C:27]([C:26]1[CH:29]=[CH:30][C:23]([N:20]2[C:16](=[O:36])[C:11]3([CH2:15][CH2:14][CH2:13][CH2:12]3)[N:10]([C:7]3[CH:8]=[CH:9][C:4]([C:3]([NH:2][CH3:1])=[O:19])=[C:5]([F:18])[CH:6]=3)[C:21]2=[S:22])=[CH:24][C:25]=1[C:31]([F:32])([F:34])[F:33])#[N:28].[CH3:1][NH:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:11]3([CH2:15][CH2:14][CH2:13]3)[C:16](=[O:36])[N:20]([C:23]3[CH:30]=[CH:29][C:26]([C:27]#[N:28])=[C:25]([C:31]([F:32])([F:34])[F:33])[CH:24]=3)[C:21]2=[S:22])=[CH:6][C:5]=1[F:18])=[O:19]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 59296600N-Methyl 2-fluoro-4-(1-cyanocyclopentyl)aminobenzamide2회

생성물 2

HCID 119577564-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide수율 7%HCID 159516244-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4,4]nonan-1-yl)-2-fluoro-N-methylbenzamide

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
130 °C

실험 절차

A mixture of N-Methyl 2-fluoro-4-(1-cyanocyclopentyl)aminobenzamide (Formula 43) (57 mg, 0.22 mmol) and 4-isothiocyanato-2-trifluoromethyl benzonitrile (0.15 g, 0.65 mmol) in DMF (3 mL) was heated under microwave irradiation (open vessel) at 130° C. for 12 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-(3-(4-Cyano-3-(trifluoromethyl)phenyl)-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluoro-N-methylbenzamide, RD162″ (Formula 44) (8 mg, 7%) as a pale yellowish solid. 1H NMR δ 8.28 (dd, 1H, J=8.4, 8.4 Hz), 7.98 (d, 1H, J=8.3 Hz), 7.96 (d, 1H, J=1.8 Hz), 7.84 (dd, 1H, J=8.3, 1.8 Hz), 7.27 (dd, 1H, J=8.4, 1.8 Hz), 7.17 (dd, 1H, J=11.7, 1.8 Hz), 6.67-6.77 (m, 1H), 3.07 (d, 3H, J=4.3 Hz), 2.32-2.41 (m, 2H), 2.13-2.21 (m, 2H), 1.85-1.96 (m, 2H), 1.49-1.59 (m, 2H).

후처리

  1. temperatureThe second mixture was refluxed for 1.5 h
  2. temperatureAfter being cooled to room temperature
  3. extractionextracted with ethyl acetate (50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 95:5)

출처 및 근거

ORD 기록
ord-ab7f2224908c443a94e021e062f90853
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08183274B2

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