Dimethylformamide → 2-[2-(2,4-Dichloro-phenyl)-acetylamino]-nicotinic acid methyl ester

HRID 1042310Notes

Reaction equation

HRID 1042310 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[CH2:15][C:16]([OH:18])=O.CN(C)C=O.[CH3:24][O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][C:28]=1[NH2:33]>ClCCl.CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH3:24][O:25][C:26](=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[N:29][C:28]=1[NH:33][C:16](=[O:18])[CH2:15][C:9]1[CH:10]=[CH:11][C:12]([Cl:14])=[CH:13][C:8]=1[Cl:7]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 882092,4-Dichlorophenylacetic acidHCID 351633Methyl 2-aminopyridine-3-carboxylate

Product 1

HCID 581333852-[2-(2,4-Dichloro-phenyl)-acetylamino]-nicotinic acid methyl esterYield 44.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent3×

Procedure

Oxalyl chloride (0.14 ml) was added dropwise to a solution of (2,4-dichloro-phenyl)-acetic acid (270 mg) in dichloromethane (10 ml) at ambient temperature. A drop of N,N-dimethylformamide (“DMF”) was added to initiate the reaction. The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated to give a colourless oil which was dissolved in dichloromethane (3 ml). The mixture was added dropwise to a cooled (−5° C.) slurry of 2-amino-nicotinic acid methyl ester (200 mg) (Example 1.1), 4-dimethylaminopyridine (“DMAP”) (32 mg) and pyridine (0.19 ml) in dichloromethane (5 ml). The reaction mixture was allowed to warm to ambient temperature and stirred at ambient temperature for 16 hours. The reaction mixture was partitioned between dichloromethane and aqueous hydrochloric acid (2M). The phases were separated. The organic layer was dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: acetone/iso-hexane ratio 1:9 to 2:8) to give 2-[2-(2,4-dichloro-phenyl)-acetylamino]-nicotinic acid methyl ester as a light yellow gum (197 mg). 1H-NMR (400 MHz, CDCl3): 10.81 (bs, 1H), 8.59-8.60 (m, 1H), 8.29-8.31 (m, 1H), 7.42-7.44 (m, 1H), 7.34-7.36 (m, 1H), 7.23-7.27 (m, 1H), 7.07-7.11 (m, 1H), 4.08 (s, 2H), 3.90 (s, 3H) ppm.

Workup

  1. customthe reaction
  2. concentrationThe reaction mixture was concentrated
  3. customto give a colourless oil which
  4. additionThe mixture was added dropwise to
  5. temperatureto warm to ambient temperature
  6. stirringstirred at ambient temperature for 16 hours
  7. customThe reaction mixture was partitioned between dichloromethane and aqueous hydrochloric acid (2M)
  8. customThe phases were separated
  9. dry with materialThe organic layer was dried over magnesium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography on silica gel (eluent: acetone/iso-hexane ratio 1:9 to 2:8)

Sources & evidence

ORD record
ord-3c39a2a443ca4ac3b8fae35937c18a15
Source dataset
uspto-grants-2013_10
Patent number
US08557840B2

Reaction notes

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