6-Methyl-3-pyridinecarboxaldehyde → HCID 46842157, compound

HRID 1846361Notes

Reaction equation

HRID 1846361 reaction equation
[NH2:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]2[CH2:15][CH2:14]2)=[CH:9][CH:8]=1)=[O:5].[CH3:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=O)=[CH:23][N:22]=1>CCO>[CH:13]1([C:10]2[CH:11]=[CH:12][C:7]([N:6]3[C:4](=[O:5])[C:3]4[C:2](=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:1]=[C:25]3[C:24]3[CH:23]=[N:22][C:21]([CH3:20])=[CH:28][CH:27]=3)=[CH:8][CH:9]=2)[CH2:15][CH2:14]1

Participants

4

Reactant 2

HCID 101925666-Methyl-3-pyridinecarboxaldehydeHCID 67459390HCID 67459390, compound

Product 1

HCID 46842157HCID 46842157, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-amino-N-(4-cyclopropylphenyl)benzamide (0.342 g, 1.36 mmol), 6-methylnicotinaldehyde (0.197 g, 1.63 mmol), and anyhydrous CuCl2 (0.547 g, 4.08 mmol) were combined in anyhydrous EtOH (30 mL) and heated at reflux for 2.5 hours. After concentration, ethyl acetate (200 mL) was added, and the mixture was washed with water (2×100 mL), dried (MgSO4), filtered, and concentrated. Purification by flash chromatography on silica gel, eluting with 20% ethyl acetate/hexanes to 30% ethyl acetate/hexanes to 100% ethyl acetate, plus further purification by flash chromatography on silica gel, eluting with 1:1 ethyl acetate/CH2Cl2, afford the title compound as a white solid (0.070 g, 15%). 1H-NMR (300 MHz, DMSO-6): δ8.44 (d, J=2.0 Hz, 1H), 8.18-8.20 (m, 1H), 7.88-7.94 (m, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.58-7.65 (m, 2H), 7.22 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.1 Hz, 1H), 7.04 (d, J=8.4 Hz, 2H), 2.40 (s, 3H), 1.84-1.91 (m, 1H), 0.91-0.99 (m, 2H), 0.63-0.68 (m, 2H). MS (APCI) m/z: 354 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureat reflux for 2.5 hours
  3. concentrationAfter concentration, ethyl acetate (200 mL)
  4. additionwas added
  5. washthe mixture was washed with water (2×100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by flash chromatography on silica gel
  10. washeluting with 20% ethyl acetate/hexanes to 30% ethyl acetate/hexanes to 100% ethyl acetate, plus further purification by flash chromatography on silica gel
  11. washeluting with 1:1 ethyl acetate/CH2Cl2

Sources & evidence

ORD record
ord-c6b66e4c99ac414586afd12190f05b0a
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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