Methyl iodide → Methyl 5-[(4-fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarboxylate

HRID 2364551Notes

Reaction equation

HRID 2364551 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:10]=[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[C:12]([C:15]([OH:17])=[O:16])=[N:13][CH:14]=2)=[CH:4][CH:3]=1.[C:27](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O.C(OCC)(=O)C.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:10]=[C:11]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[C:12]([C:15]([O:17][CH3:27])=[O:16])=[N:13][CH:14]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 694827505-[(4-Fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarboxylic acid

Product 1

HCID 69482194Methyl 5-[(4-fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarboxylateYield 64%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-[(4-fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarboxylic acid (560 mg, 1.59 mmol) was dissolved in N,N-dimethylformamide (50 mL) and potassium carbonate (483 mg, 3.50 mmol) and iodomethane (0.15 mL, 2.39 mmol) were added. The reaction was stirred at ambient temperature for 3 hours, diluted with ethyl acetate and water, and extracted with ethyl acetate. The organics were dried over sodium sulfate and concentrated under reduced pressure. Purification by silica gel chromatography (20-100% ethyl acetate/hexanes gradient elution) gave methyl 5-[(4-fluorophenyl)methyl]-3-{[4-(methyloxy)phenyl]amino}-2-pyridinecarboxylate (373 mg, 64% yield) as a white solid. 1H NMR (CDCl3) δ 9.22 (s, 1 H), 7.89 (s, 1 H), 7.09-7.02 (m, 4 H), 6.96-6.86 (m, 4 H), 3.97 (s, 2 H), 3.82 (s, 3 H), 3.80 (s, 3 H); MS m/z 367 (M+1).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organics were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customPurification
  5. washby silica gel chromatography (20-100% ethyl acetate/hexanes gradient elution)

Sources & evidence

ORD record
ord-7bf254ac34ed41a4a1692f70cefc3623
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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