Potassium Carbonate → N-[4-(4-amino-2,5-difluorophenoxy)-6-chloropyrimidin-2-yl]acetamide

HRID 476361Notes

Reaction equation

HRID 476361 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.[Cl:11][C:12]1[CH:17]=[C:16](Cl)[N:15]=[C:14]([NH:19][C:20](=[O:22])[CH3:21])[N:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][C:16]2[CH:17]=[C:12]([Cl:11])[N:13]=[C:14]([NH:19][C:20](=[O:22])[CH3:21])[N:15]=2)=[C:4]([F:10])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27787624-Amino-2,5-difluorophenolHCID 12611964N-(4,6-Dichloropyrimidin-2-yl)acetamide

Product 1

HCID 86662870N-[4-(4-amino-2,5-difluorophenoxy)-6-chloropyrimidin-2-yl]acetamideYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 4-amino-2,5-difluoro-phenol (3.5 g, 24 mmol), N-(4,6-dichloro-pyrimidin-2-yl)-acetamide (5.30 g, 24 mmol) and potassium carbonate (3.4 g, 24 mmol) in DMF (100 mL) was stirred at 50° C. under nitrogen overnight. After cooling to room temperature the reaction mixture was suspended in water (300 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers was washed with brine, dried over sodium sulfate and concentrated. The crude product was purified by silica gel chromatography (15%-20% ethyl acetate in petroleum ether) to give N-[4-(4-amino-2,5-difluoro-phenoxy)-6-chloro-pyrimidin-2-yl]-acetamide (3.3 g, 44% yield) as a white solid. 1HNMR (400 MHz, DMSO-d6): δ 10.72 (s, 1H), 7.20-7.24 (dd, J=11.2 Hz, J=7.6 Hz, 1H), 7.00 (s, 1H), 6.64 (dd, J=12.0 Hz, J=8.4 Hz, 1H), 5.48 (s, 2H), 2.03 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×200 mL)
  2. washThe combined organic layers was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography (15%-20% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-dc9a2079720c431098d0573e8fa3522f
Source dataset
uspto-grants-2014_01
Patent number
US08637672B2

Reaction notes

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