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

HRID 560810Notes

Reaction equation

HRID 560810 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:17][C:16]([C:18](O)=[O:19])=[C:15]([CH3:21])[CH:14]=3)[CH:9]=[N:8]2)=[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.[NH2:55][CH2:56][C:57]1[CH:58]=[N:59][CH:60]=[CH:61][CH:62]=1>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[C:11](=[O:12])[N:10]([C:13]3[S:17][C:16]([C:18]([NH:55][CH2:56][C:57]4[CH:58]=[N:59][CH:60]=[CH:61][CH:62]=4)=[O:19])=[C:15]([CH3:21])[CH:14]=3)[CH:9]=[N:8]2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 594811895-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-3-methylthiophene-2-carboxylic acid

Product 1

HCID 594812615-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamideYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 5-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-3-methylthiophene-2-carboxylic acid (0.13 g, 0.38 mmol), 1-hydroxybenzotriazole (0.077 g, 0.57 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.11 g, 0.57 mmol) in N,N-dimethylformamide (2 mL) was added N,N-diisopropylethylamine (0.20 mL, 1.14 mmol) and 3-(aminomethyl)pyridine (0.04 mL, 0.39 mmol). The resulting reaction mixture was stirred for 18 h at ambient temperature, then diluted with ethyl acetate (75 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution (3×35 mL) and water (35 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with dichloromethane in hexanes to afford the title compound as a colorless solid in 87% yield (0.14 g): mp 180-182° C.: 1H NMR (300 MHz, CDCl3) δ 8.59 (s, 1H), 8.52 (d, J=4.1 Hz, 1H), 7.72 (s, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.39-7.33 (m, 2H), 7.30-7.24 (m, 1H), 7.06-6.98 (m, 2H), 6.87 (s, 1H), 6.43 (t, J=5.6 Hz, 1H), 4.95 (s, 2H), 4.59 (d, J=5.6 Hz, 2H), 2.50 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 162.64 (d, JC-F=247.1 Hz), 162.6, 150.4, 149.3, 149.1, 140.8, 135.7, 134.5, 133.7, 132.3, 131.2 (d, JC-F=3.2 Hz), 130.3 (d, JC-F=8.3 Hz), 125.3, 123.7, 120.2, 115.8 (d, JC-F=21.6 Hz), 49.0, 41.5, 16.0; MS (ES+) m/z 424.3 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution (3×35 mL) and water (35 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with dichloromethane in hexanes

Sources & evidence

ORD record
ord-0b20994ea5cb4772907a846303a6f520
Source dataset
uspto-grants-2011_11
Patent number
US08063084B2

Reaction notes

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