4-Fluoroaniline → N-(4-fluorophenyl)-2-(methylthio)-5-pyrimidinecarboxamide

HRID 348433Notes

Reaction equation

HRID 348433 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1.C([O:17][C:18]([C:20]1[CH:21]=[N:22][C:23]([S:26][CH3:27])=[N:24][CH:25]=1)=O)C>C1COCC1>[F:7][C:8]1[CH:14]=[CH:13][C:11]([NH:12][C:18]([C:20]2[CH:21]=[N:22][C:23]([S:26][CH3:27])=[N:24][CH:25]=2)=[O:17])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 97314-FluoroanilineHCID 10442716Ethyl 2-(methylthio)pyrimidine-5-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 58802987N-(4-fluorophenyl)-2-(methylthio)-5-pyrimidinecarboxamideYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of potassium tert-butoxide (1 M in THF, 66 mL, 66 mmol) in THF (66 mL) in an ice bath was added 4-fluoroaniline over 1.5 min. The solution was stirred for 1 min, then a solution of 2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester (3.745 g, 18.9 mmol) in THF (30 mL) was added via syringe over 4 min. The syringe was washed with 4 mL THF, and the reaction allowed to proceed for 5 min. The reaction was quenched with 1% HCl (450 mL) resulting in a solid precipitate. The solution was filtered, and the solids washed with water. After drying, the solids were triturated with 10% ethyl acetate/hexane to afford 4.0 g (80% yield) of the titled product as a pale yellow solid, which was used in the following preparations.

Workup

  1. washThe syringe was washed with 4 mL THF
  2. waitto proceed for 5 min
  3. customThe reaction was quenched with 1% HCl (450 mL)
  4. customresulting in a solid precipitate
  5. filtrationThe solution was filtered
  6. washthe solids washed with water
  7. customAfter drying
  8. customthe solids were triturated with 10% ethyl acetate/hexane

Sources & evidence

ORD record
ord-780dec1ec89544dba5ab5d5f42266151
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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