Benzylamine → N-benzyl-2-chloropyridine-4-carboxamide

HRID 714275Notes

Reaction equation

HRID 714275 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=O.[CH2:11]([NH2:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>S(Cl)(Cl)=O.ClCCl>[CH2:11]([NH:18][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][N:10]=[C:2]([Cl:1])[CH:3]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 7504BenzylamineHCID 8471TriethylamineHCID 2369852-Chloroisonicotinic acid

Product 1

HCID 15115857N-benzyl-2-chloropyridine-4-carboxamideYield 68.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 2-chloroisonicotinic acid (5.00 g, 31.7 mmol) in thionyl chloride (25 mL) was refluxed for 30 minutes and concentrated in vacuo to dryness. The residue was dissolved in dichloromethane (100 mL) and added to a mixture of benzylamine (3.40 g, 31.7 mmol) and triethylamine (6.64 mL, 47.6 mmol) in dichloromethane (40 mL). The resulting solution was stirred at ambient temperature for 16 hours, washed with saturated sodium bicarbonate solution (30 mL), water (30 mL) and brine (30 mL). The separated organic solution was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with 60-80% ethyl acetate in hexanes to give N-benzyl-2-chloroisonicotinamide as a colorless solid (5.35 g, 49%): 1H NMR (300 MHz, DMSO-d6) δ 9.44-9.40 (m, 1H), 8.56 (d, J=5.1 Hz, 1H), 7.91 (s, 1H), 7.82-7.80 (m, 1H), 7.34-7.25 (m, 5H), 4.49 (d, J=5.1 Hz, 2H), MS (ES+) m/z 247.2 (M+1).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  3. washwashed with saturated sodium bicarbonate solution (30 mL), water (30 mL) and brine (30 mL)
  4. dry with materialThe separated organic solution was dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with 60-80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d77140eeade04212b1e30ef868a53947
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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