Water → Methyl 6-chloro-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate

HRID 2092754Notes

Reaction equation

HRID 2092754 reaction equation
Cl[C:2]1[N:11]=[C:10]([Cl:12])[CH:9]=[C:8]([C:13]#[N:14])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[F:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][C:17]=1[CH3:23].CCN(CC)CC.O>C(#N)C.CCOC(C)=O>[Cl:12][C:10]1[CH:9]=[C:8]([C:13]#[N:14])[C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([NH:20][C:19]2[CH:21]=[CH:22][C:16]([F:15])=[C:17]([CH3:23])[CH:18]=2)[N:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 679814-Fluoro-m-toluidineHCID 58317683Methyl 2,6-dichloro-4-cyanonicotinate

Product 1

HCID 58317541Methyl 6-chloro-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 2,6-dichloro-4-cyanonicotinate (500 mg, 2.164 mmol), 4-fluoro-3-methylaniline (325 mg, 2.60 mmol) and Et3N (0.452 mL, 3.25 mmol) in ACN (5 mL) was stirred at 50° C. for 24 h. Water and EtOAc were added to the mixture and the aqueous phase was extracted with EtOAc. The organic phases were combined, washed with H2O and brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 to give the title compound, which contains some starting material and was used without further purification (390 mg). [M+H] calc'd for C15H11ClFN3O2, 320. found, 320.

Workup

  1. extractionthe aqueous phase was extracted with EtOAc
  2. washwashed with H2O and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by chromatography on SiO2

Sources & evidence

ORD record
ord-276b04cc3e4e4c35a2cf3e69a15f48b4
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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