Chlorosuccinimide → N-(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide

HRID 1803415ノート

反応式

HRID 1803415 の反応式
[F:1][C:2]([F:19])([F:18])[C:3]([N:5]([CH3:17])[C:6]1[S:10][C:9]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[N:8][CH:7]=1)=[O:4].[Cl:20]N1C(=O)CCC1=O>C(#N)C>[Cl:20][C:7]1[N:8]=[C:9]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[S:10][C:6]=1[N:5]([CH3:17])[C:3](=[O:4])[C:2]([F:18])([F:1])[F:19]

参加物

4

反応物 2

HCID 31398Chlorosuccinimide2 回HCID 595807572,2,2-trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide

生成物 1

HCID 59580860N-(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
63 °C

実験手順

A suspension of 2,2,2-trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide (1.0 g, 3.5 mmol) and N-chlorosuccinimide (0.557 g, 4.2 mmol) in acetonitrile (30 mL) was heated to 63° C. under nitrogen for 3 h. The reaction mixture was cooled to room temperature and it was treated with additional N-chlorosuccinimide (0.557 g, 4.2 mmol) and heated to 35° C. under nitrogen for 2 h. The reaction mixture was cooled and concentrated under reduced pressure. The residue was redissolved in dichloromethane (80 mL) and washed with water (70 mL). The aqueous layer was re-extracted with methylene chloride (100 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, concentrated under reduced pressure and purified using reverse phase chromatography. The product eluted with a gradient of acetonitrile in water. The desired product was isolated as a thick brown gum (0.337 g, 30%): 1H NMR (400 MHz, CDCl3) δ 9.12 (br, 1H), 8.75 (br, 1H), 8.22 (d, J=7.9 Hz, 1H), 7.28 (br, 1H), 3.40 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −69.3; ESIMS m/z 324.3 (M+2); IR (thin film) 1772 cm−1.

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperatureheated to 35° C. under nitrogen for 2 h
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was redissolved in dichloromethane (80 mL)
  6. washwashed with water (70 mL)
  7. extractionThe aqueous layer was re-extracted with methylene chloride (100 mL)
  8. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. custompurified
  13. washThe product eluted with a gradient of acetonitrile in water

出典と根拠

ORDレコード
ord-bdabc17f9b964ef29d308265d561a98c
出典データセット
uspto-grants-2013_01
特許番号
US08350044B2

反応ノート

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