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

HRID 533298Notes

Reaction equation

HRID 533298 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
63 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3f3d58c96aea48c19cf1fd3145f6a009
Source dataset
uspto-grants-2014_10
Patent number
US08853246B2

Reaction notes

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