HCID 86760395, compound → N-(4-Fluorophenyl)-2-(2-oxobutoxy)pyrimidine-5-carboxamide

HRID 348483Notes

Reaction equation

HRID 348483 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH:12]=[N:13][C:14]([O:17][CH2:18][C:19](=[O:24])NCOC)=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.[CH2:25]([Mg]Br)[CH3:26]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:16]=[N:15][C:14]([O:17][CH2:18][C:19](=[O:24])[CH2:25][CH3:26])=[N:13][CH:12]=2)=[O:10])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 86760395HCID 86760395, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 71423461N-(4-Fluorophenyl)-2-(2-oxobutoxy)pyrimidine-5-carboxamideYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-[(Methoxymethylcarbamoyl)methoxy]pyrimidine-5-carboxylic acid (4-fluorophenyl)amide (prepared as in Example 4, 60 mg, 0.18 mmol) was suspended in 1.8 mL THF and cooled to 0° C. Ethyl magnesium bromide (1 M in THF, 0.45 mL, 0.45 mmol) was added dropwise while maintaining internal reaction temperature between 0° C. and 5° C. The reaction mixture was warmed to ambient temperature and held for 1 h. The reaction mixture was cooled back to 0° C. and a second addition (0.45 mL, 0.45 mmol) of Grignard reagent was performed. The reaction was warmed to ambient temperature and held for 2.5 hours. The reaction was quenched with 0.1 M HCl and diluted with ethyl acetate. The organic layer was separated, dried using Na2SO4 and concentrated to 36 mg of yellow oil. The crude material was purified by SiO2 chromatography to deliver 8 mg (15% yield) of the titled compound. ESI-MS m/z 304 (MH+), 302 (M−H−).

Workup

  1. temperaturewhile maintaining internal reaction temperature between 0° C. and 5° C
  2. temperatureThe reaction mixture was warmed to ambient temperature
  3. temperatureThe reaction mixture was cooled back to 0° C.
  4. temperatureThe reaction was warmed to ambient temperature
  5. waitheld for 2.5 hours
  6. customThe reaction was quenched with 0.1 M HCl
  7. additiondiluted with ethyl acetate
  8. customThe organic layer was separated
  9. customdried
  10. concentrationconcentrated to 36 mg of yellow oil
  11. customThe crude material was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-f8da27ff0dc6485bb20b85dc7b5c6277
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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