3-Pyridinemethanamine → 5-(5-benzyl-1H-1,2,4-triazol-3-yl)-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide

HRID 2381861Notes

Reaction equation

HRID 2381861 reaction equation
[CH2:1]([C:8]1[NH:12][N:11]=[C:10]([C:13]2[S:17][C:16]([C:18]([OH:20])=O)=[C:15]([CH3:21])[CH:14]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.[NH2:53][CH2:54][C:55]1[CH:56]=[N:57][CH:58]=[CH:59][CH:60]=1>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([C:8]1[NH:12][N:11]=[C:10]([C:13]2[S:17][C:16]([C:18]([NH:53][CH2:54][C:55]3[CH:56]=[N:57][CH:58]=[CH:59][CH:60]=3)=[O:20])=[C:15]([CH3:21])[CH:14]=2)[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 591797135-(5-benzyl-1H-1,2,4-triazol-3-yl)-3-methylthiophene-2-carboxylic acid

Product 1

HCID 249578555-(5-benzyl-1H-1,2,4-triazol-3-yl)-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamideYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 5-(5-benzyl-1H-1,2,4-triazol-3-yl)-3-methylthiophene-2-carboxylic acid (0.13 g, 0.43 mmol), 1-hydroxybenzotriazole (0.088 g, 0.65 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.13 g, 0.65 mmol) in anhydrous N,N-dimethylformamide (2 mL) was added N,N-diisopropylethylamine (0.23 mL, 1.30 mmol), followed by the addition of 3-(aminomethyl)pyridine (0.044 mL, 0.44 mmol). The resulting reaction mixture was stirred at ambient temperature for 18 h, and diluted with ethyl acetate (75 mL). The organic layer was washed with saturated aqueous sodium bicarbonate (3×35 mL) and water (35 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 10% methanol in dichloromethane to afford the title compound as a colorless foam (0.11 g, 67%): mp 82° C. (dec.); 1H NMR (300 MHz, DMSO-d6) δ 8.66 (t, J=5.6 Hz, 1H), 8.55 (s, 1H), 8.46 (s, 1H), 7.73 (d, J=7.9 Hz, 1H), 7.42-7.20 (m, 8H), 4.44 (d, J=5.6 Hz, 2H), 4.10 (s, 2H), 2.43 (s, 3H); MS (ES+) m/z 390.3 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate (3×35 mL) and water (35 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluted with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-24cfe45382cd44768457ff343c84c569
Source dataset
uspto-grants-2012_09
Patent number
US08258160B2

Reaction notes

Loading…