Water → Methyl 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

HRID 2364528Notes

Reaction equation

HRID 2364528 reaction equation
[CH:1]1([NH:4][C:5]2[C:6]([C:19]([OH:21])=[O:20])=[N:7][CH:8]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:3][CH2:2]1.[C:22](=O)([O-])[O-].[K+].[K+].CI.O>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([NH:4][C:5]2[C:6]([C:19]([O:21][CH3:22])=[O:20])=[N:7][CH:8]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 694804773-(Cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid

Product 1

HCID 69481047Methyl 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylateYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid (298 mg, 1.1 mmol) in DMF (10 mL) was added potassium carbonate (316 mg, 2.3 mmol) followed by methyl iodide (0.15 mL, 2.3 mmol). The resultant suspension was stirred for 1.5 hours at which time water and ethyl acetate were added. The layers were separated and the organic layer was washed with brine. The aqueous layer was extracted with ethyl acetate and the combined organics were dried over sodium sulphate. Filtration and concentration followed by purification by silica gel chromatography provided methyl 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (234 mg, 77%) as a white crystalline solid upon standing. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J=1.9 Hz, 1 H), 7.78 (br, 1 H), 7.24 (s, 1 H), 7.15 (dd, J=8.5, 5.4 Hz, 2 H), 7.00 (t, J=8.7 Hz, 2 H), 3.96 (s, 2 H), 3.93 (s, 3 H), 2.39 (m, 1 H), 0.77 (m, 2 H), 0.52 (m, 2 H); MS m/z 301 (M+1).

Workup

  1. additionwere added
  2. customThe layers were separated
  3. washthe organic layer was washed with brine
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organics were dried over sodium sulphate
  6. filtrationFiltration and concentration
  7. customfollowed by purification by silica gel chromatography

Sources & evidence

ORD record
ord-863cb6821c464aaf8f68a4a4ff02bf87
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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