Toluene → 1-[5-(4-Fluoro phenyl)-2-methyl-thiazol-4-yl]-1-{(S)-2-[(5-trifluoromethyl-pyrimidin-2-ylamino)-methyl]-pyrrolidin-1-yl}-methanone

HRID 18110

反応式

HRID 18110 の反応式
Br[C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([C:17]2[N:18]=[C:19]([CH3:29])[S:20][C:21]=2[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)=[O:16])=[N:6][CH:7]=1.[F:30][C:31]([F:36])([F:35])C([O-])=O.[K+].C1(C)C=CC=CC=1.O.CCOCC>CN(C)C=O.[Cu](I)I>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:21]2[S:20][C:19]([CH3:29])=[N:18][C:17]=2[C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@H:10]2[CH2:9][NH:8][C:5]2[N:4]=[CH:3][C:2]([C:31]([F:36])([F:35])[F:30])=[CH:7][N:6]=2)=[O:16])=[CH:23][CH:24]=1

参加物

7

反応物 4

HCID 1140TolueneHCID 21584184Diethylether waterHCID 23662811Potassium trifluoroacetateHCID 670897411-{(S)-2-[(5-Bromo-pyrimidin-2-ylamino)methyl]-pyrrolidin-1-yl}-1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanone

生成物 1

HCID 670903201-[5-(4-Fluoro phenyl)-2-methyl-thiazol-4-yl]-1-{(S)-2-[(5-trifluoromethyl-pyrimidin-2-ylamino)-methyl]-pyrrolidin-1-yl}-methanone収率 0.3%

試薬・触媒・溶媒 2

HCID 83717Copper iodide触媒HCID 6228Dimethylformamide溶媒

実験手順

To the compound from Example 194 (0.36 g) in dimethylformamide (5 ml) was added potassium trifluoroacetate (0.23 g), copper iodide (0.3 g) and toluene (5 ml) and the resulting mixture heated at reflux under Dean-Stark conditions for 3 h, before refluxing for a further 20 h. The reaction mixture was cooled, poured into water/ether and filtered through kieselguhr. The aqueous layer from the filtrate was extracted with ether, and the combined ether extracts washed with water, dried and evaporated. The aqueous was re-extracted with dichloromethane and the extract evaporated. The combined extracts were chromatographed on silica gel, eluting with methanol-dichloromethane mixtures, to afford the title product (0.001 g). Mass Spectrum (Electrospray LC/MS): Found 466 (MH+). C21H19F4N5OS requires 465.

後処理

  1. temperaturethe resulting mixture heated
  2. temperatureat reflux under Dean-Stark conditions for 3 h
  3. temperaturebefore refluxing for a further 20 h
  4. temperatureThe reaction mixture was cooled
  5. filtrationfiltered through kieselguhr
  6. extractionThe aqueous layer from the filtrate was extracted with ether
  7. washthe combined ether extracts washed with water
  8. customdried
  9. customevaporated
  10. extractionThe aqueous was re-extracted with dichloromethane
  11. customthe extract evaporated
  12. customThe combined extracts were chromatographed on silica gel
  13. washeluting with methanol-dichloromethane mixtures

出典と根拠

ORDレコード
ord-4ef542aa7a634e42a6b1cfff2811ea52
出典データセット
uspto-grants-2010_06
特許番号
US07741329B2

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