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 245022ノート

反応式

HRID 245022 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-69131a4039d54a80997a82970c75b725
出典データセット
uspto-grants-2014_02
特許番号
US08658681B2

反応ノート

読み込み中…