4-Fluoroaniline → N-(4-fluorophenyl)-2-chloro-pyrimidinamide

HRID 869282Notes

Reaction equation

HRID 869282 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5](C(O)=O)=[CH:4][N:3]=1.[C:11](Cl)(=[O:15])C(Cl)=O.[F:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1>ClCCl.CN(C)C=O>[F:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:11]([C:2]2([Cl:1])[N:3]=[CH:4][CH:5]=[CH:6][NH:7]2)=[O:15])=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 97314-FluoroanilineHCID 65578Oxalyl chlorideHCID 110949062-Chloropyrimidine-5-carboxylic acid

Product 1

HCID 117844382N-(4-fluorophenyl)-2-chloro-pyrimidinamideYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

2-Chloro-pyrimidine-5-carboxylic acid 1 (3.16 g, 20 mmol) was suspended in dichloromethane (40 mL), and oxalyl chloride (3.30 g, 26 mmol) was added, followed by dimethylformamide (3 drops) as catalyst. The reaction started to vigorously evolve gas. The reaction was heated to reflux for 1 hour, then allowed to cool to room temperature. 4-fluoroaniline was added, vigorous bubbling was seen again, and the reaction mixture warmed up considerably. Triethylamine was added, and a flocculent precipitate immediately formed. The reaction mixture was heated to reflux once again for another hour, removed from heat, and stirred at room temperature for 18 hours under nitrogen. The reaction was diluted with ethyl acetate (100 mL), and the organic layer washed with water, saturated sodium bicarbonate, water, 1N HCl, water, saturated sodium chloride, then dried over sodium sulfate. The liquid was filtered, and evaporated to yield 3.44 g (68%) of compound 3 as a light yellow solid. ESI-MS m/z=252.0 [M+H]+.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1 hour
  3. customvigorous bubbling
  4. temperaturethe reaction mixture warmed up considerably
  5. additionTriethylamine was added
  6. customa flocculent precipitate immediately formed
  7. temperatureThe reaction mixture was heated
  8. temperatureto reflux once again for another hour
  9. customremoved
  10. temperaturefrom heat
  11. additionThe reaction was diluted with ethyl acetate (100 mL)
  12. washthe organic layer washed with water, saturated sodium bicarbonate, water, 1N HCl, water, saturated sodium chloride
  13. dry with materialdried over sodium sulfate
  14. filtrationThe liquid was filtered
  15. customevaporated

Sources & evidence

ORD record
ord-b4b97cbb4953459880f4e872719d041e
Source dataset
uspto-grants-2015_03
Patent number
US08969365B2

Reaction notes

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