Triethylamine → 2-[(2-Chloro-pyridine-4-carbonyl)-amino]-nicotinic acid methyl ester

HRID 602424Notes

Reaction equation

HRID 602424 reaction equation
[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[NH2:10].C(N(CC)CC)C.[Cl:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][N:28]=1)[C:23](Cl)=[O:24]>ClCCl>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[NH:10][C:23]([C:22]1[CH:26]=[CH:27][N:28]=[C:20]([Cl:19])[CH:21]=1)=[O:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 351633Methyl 2-aminopyridine-3-carboxylateHCID 28000032-Chloropyridine-4-carbonyl chloride

Product 1

HCID 586749492-[(2-Chloro-pyridine-4-carbonyl)-amino]-nicotinic acid methyl esterYield 60.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A stirred and chilled (0° C.) mixture of 2-amino-nicotinic acid methyl ester (11 g, 72.3 mmol) in dichloromethane was treated sequentially with triethylamine (11 mL, 79.5 mmol) and a solution of 2-chloro-isonicotinoyl chloride (12.73 g, 72.3 mmol) in dichloromethane, such that the total volume of solvent was 80 mL. The reaction was warmed to room temperature and on completion of the reaction was quenched by addition of water. The aqueous phase was separated and extracted with EtOAc. The combined organic phases were washed with brine, dried and concentrated in vacuo. The residue was suspended in hot hexane, filtered while hot and the resulting solid recrystallised from EtOH, to give 2-[(2-chloro-pyridine-4-carbonyl)-amino]-nicotinic acid methyl ester (12.76 g); 1H-NMR (300 MHz, d6-DMSO) 11.47 (1H, s), 8.62-8.67 (2H, m), 8.20 (1H, unresolved dd), 7.99 (1H, s), 7.89 (1H, unresolved dd), 7.43 (1H, dd), 3.72 (3H, s).

Workup

  1. temperaturechilled
  2. customwas quenched by addition of water
  3. customThe aqueous phase was separated
  4. extractionextracted with EtOAc
  5. washThe combined organic phases were washed with brine
  6. customdried
  7. concentrationconcentrated in vacuo
  8. filtrationfiltered while hot and the resulting solid
  9. customrecrystallised from EtOH

Sources & evidence

ORD record
ord-a6e38a75c00548379fe8b536e71a278d
Source dataset
uspto-grants-2011_03
Patent number
US07906533B2

Reaction notes

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