反応 #2286374

ord-ac5a5ecda3dc4cfda13571153c50f3c1

反応方程式

CN(C(=O)C(F)(F)F)c1cnc(-c2cccnc2)s1
2,2,2-trifluoro-N-methyl-N-(2-pyridin-3-yl-thiazol-5-yl)-acetamide
O=C1CCC(=O)N1Cl
N-chlorosuccinimide
O=C1CCC(=O)N1Cl
N-chlorosuccinimide
CN(C(=O)C(F)(F)F)c1sc(-c2cccnc2)nc1Cl
desired product
CN(C(=O)C(F)(F)F)c1sc(-c2cccnc2)nc1Cl
N-(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-2,2,2-trifluoro-N-methyl-acetamide

反応条件

温度
63°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度The reaction mixture was cooled to room temperature
  2. 2
    温度heated to 35° C. under nitrogen for 2 h
  3. 3
    温度The reaction mixture was cooled
  4. 4
    濃縮concentrated under reduced pressure
  5. 5
    workup.DISSOLUTIONThe residue was redissolved in dichloromethane (80 mL)
  6. 6
    洗浄washed with water (70 mL)
  7. 7
    抽出The aqueous layer was re-extracted with methylene chloride (100 mL)
  8. 8
    洗浄The combined organic layers were washed with water (50 mL) and brine (50 mL)
  9. 9
    乾燥dried over sodium sulfate
  10. 10
    ろ過filtered
  11. 11
    濃縮concentrated under reduced pressure
  12. 12
    その他purified
  13. 13
    洗浄The product eluted with a gradient of acetonitrile in water

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.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09357780B2uspto-grants-2016_06