Potassium Carbonate → HCID 67980878, compound

HRID 1427439Notes

Reaction equation

HRID 1427439 reaction equation
Cl.[I:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([NH2:14])[CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:5][CH:4]=1.F[C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][N:17]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.C(OCC)(=O)C>[I:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([NH:14][C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][N:17]=2)[CH2:10][CH:11]([CH3:12])[CH3:13])=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 13758765Methyl 6-fluoropyridine-3-carboxylateHCID 67980801HCID 67980801, compound

Product 1

HCID 67980878HCID 67980878, compoundYield 52.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

1-(4-Iodophenyl)-3-methylbutan-1-amine hydrochloride (1.14 g, 3.49 mmol), methyl 6-fluoronicotinate (0.568 g, 3.66 mmol), and potassium carbonate (1.45 g, 10.5 mmol) were combined in N,N-dimethylformamide (11.6 mL) and heated to 100° C. for 3.5 hours. The reaction was then cooled to room temperature and diluted with water and ethyl acetate. The layers were separated and the aqueous was extracted 3 times with ethyl acetate. The combined organics were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by column chromatography (0-30% ethyl acetate/heptane) provided methyl 6-(1-(4-iodophenyl)-3-methylbutylamino)nicotinate (0.772 g, 52%) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 8.69 (d, J=1.8 Hz, 1H), 7.89 (dd, J=8.8, 2.3 Hz, 1H), 7.60-7.64 (m, 2H), 7.04-7.08 (m, 2H), 6.16 (d, J=8.4 Hz, 1H), 5.49 (d, J=6.4 Hz, 1H), 4.62-4.69 (m, 1H), 3.82 (s, 3H), 1.54-1.76 (m, 3H), 0.90-0.97 (m, 6H). MS (M+1): 425.2.

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous was extracted 3 times with ethyl acetate
  4. washThe combined organics were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (0-30% ethyl acetate/heptane)

Sources & evidence

ORD record
ord-20f5fb89fb5c4ea0aa2f3b658aab69fd
Source dataset
uspto-grants-2015_01
Patent number
US08933104B2

Reaction notes

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