Cyclohexylamine → 3-Ethyl 5-methyl 2-(cyclohexylamino)-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylate

HRID 1912593Notes

Reaction equation

HRID 1912593 reaction equation
F[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[C:5]([C:20]([O:22][CH3:23])=[O:21])=[C:4]([CH3:24])[N:3]=1.[CH:25]1([NH2:31])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.C(N(CC)CC)C>ClCCCl>[CH:25]1([NH:31][C:2]2[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=3)[C:5]([C:20]([O:22][CH3:23])=[O:21])=[C:4]([CH3:24])[N:3]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 7965CyclohexylamineHCID 8471TriethylamineHCID 71209155Ethyl 5-methyl 2-fluoro-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylate

Product 1

HCID 712094953-Ethyl 5-methyl 2-(cyclohexylamino)-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylateYield 116%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Ethyl 5-methyl 2-fluoro-6-methyl-4-(p-tolyl)pyridine-3,5-dicarboxylate (14 mg, 0.042 mmol) was dissolved in DCE (1 mL). Cyclohexylamine (9.67 ul, 0.085 mmol) and triethylamine (5.89 ul, 0.042 mmol) were added and the reaction was heated at reflux 18 hours. The mixture was concentrated, diluted with ethyl acetate and brine, extracted with ethyl acetate, dried over sodium sulfate, and concentrated to afford the title compound (20 mg) that was used without further purification: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.08-7.15 (m, 2 H) 6.97-7.07 (m, 2 H) 4.04-4.19 (m, 1 H) 3.75-3.88 (m, 2 H) 3.41 (s, 3 H) 2.43 (s, 3 H) 2.35 (s, 3 H) 1.96-2.17 (m, 2 H) 1.55-1.93 (m, 4 H) 1.36-1.53 (m, 2 H) 1.17-1.37 (m, 2 H) 0.56-0.71 (m, 3 H); LCMS (m/z) ES+=411 (M+1).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux 18 hours
  3. concentrationThe mixture was concentrated
  4. additiondiluted with ethyl acetate and brine
  5. extractionextracted with ethyl acetate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-89aa026d624c4f43a3bd1b90d71fb1b7
Source dataset
uspto-grants-2013_12
Patent number
US08609653B2

Reaction notes

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