Water → Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate

HRID 515974Notes

Reaction equation

HRID 515974 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].C(N(CC)CC)C.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[CH:24]=1.O>C1COCC1>[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:22][C:23]2[CH:24]=[C:25]([CH3:29])[CH:26]=[CH:27][CH:28]=2)[N:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7934m-ToluidineHCID 8471TriethylamineHCID 58317683Methyl 2,6-dichloro-4-cyanonicotinate

Product 1

HCID 58317587Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinateYield 33.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl 2,6-dichloro-4-cyanonicotinate (455 mg, 1.97 mmol), triethylamine (0.549 mL, 3.94 mmol) and m-toluidine (0.32 mL, 2.95 mmol) in THF (10 mL) was stirred at RT for 3 days. Water was added to the resulting 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 as a yellow solid (198 mg, 33.3%). 1H NMR (500 MHz, CDCl3) δ ppm 2.40 (s, 3 H), 3.99 (s, 3H), 6.92 (s, 1H), 7.05-7.14 (m, 4H), 7.33 (t, J=7.81 Hz, 1H).

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-4eddae5bd05c4b7494c637f5503548b4
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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