Triethylamine → 2-benzamido-N-(4-(trifluoromethyl)benzyl)-isonicotinamide

HRID 714301Notes

Reaction equation

HRID 714301 reaction equation
[C:1]([NH:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][N:18]=1)[C:13]([OH:15])=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH2:28])=[CH:23][CH:22]=1.C(N(CC)CC)C>S(Cl)(Cl)=O.ClCCl>[C:1]([NH:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][N:18]=1)[C:13]([NH:28][CH2:27][C:24]1[CH:23]=[CH:22][C:21]([C:20]([F:19])([F:29])[F:30])=[CH:26][CH:25]=1)=[O:15])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 768044-(Trifluoromethyl)benzylamineHCID 643938512-Benzamidoisonicotinic acid

Product 1

HCID 671538362-benzamido-N-(4-(trifluoromethyl)benzyl)-isonicotinamideYield 8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 2-benzamidoisonicotinic acid (0.18 g, 0.74 mmol) in thionyl chloride (10 mL) was refluxed for 30 minutes and concentrated in vacuo to dryness. The residue was dissolved in dichloromethane (25 mL) and added to a mixture of (4-(trifluoromethyl)phenyl)methanamine (0.13 g, 0.74 mmol) and triethylamine (0.31 mL, 2.23 mmol) in dichloromethane (20 mL). The reaction mixture was stirred at ambient temperature for 30 minutes, washed with saturated sodium bicarbonate solution (30 mL), water (30 mL) and brine (30 mL), then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 30-45% ethyl acetate in hexanes to give 2-benzamido-N-(4-(trifluoromethyl)benzyl)-isonicotinamide as a colorless solid (0.02 g, 8%): mp 165-168° C. (dichloromethane/hexanes); 1H NMR (300 MHz, CDCl3) δ 8.79 (br s, 2H), 8.66 (s, 1H), 7.89-7.86 (m, 2H), 7.59-7.44 (m, 8H), 7.05-7.03 (m, 1H), 4.69 (d, J=6.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 166.0, 165.4, 152.1, 149.1, 143.7, 141.7, 133.6, 132.7, 129.0 (2 peaks), 128.1 (2 peaks), 127.2 (2 peaks), 125.8, 125.7, 118.7, 110.3, 43.7; MS (ES+) m/z 400.4 (M+1).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. dissolutionThe residue was dissolved in dichloromethane (25 mL)
  3. washwashed with saturated sodium bicarbonate solution (30 mL), water (30 mL) and brine (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography
  8. washeluted with 30-45% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e42a114bfd54475b956f4bbf563c675d
Source dataset
uspto-grants-2015_11
Patent number
US09187426B2

Reaction notes

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