3-Pyridinemethanamine → 2-(3-(2-(4-fluorobenzylamino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamide

HRID 554971Notes

Reaction equation

HRID 554971 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][NH:7][C:8](=[O:25])[CH2:9][N:10]2[CH2:14][CH2:13][N:12]([C:15]3[S:16][C:17]([C:21]([OH:23])=O)=[C:18]([CH3:20])[N:19]=3)[C:11]2=[O:24])=[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.[NH2:59][CH2:60][C:61]1[CH:62]=[N:63][CH:64]=[CH:65][CH:66]=1>CN(C)C=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8](=[O:25])[CH2:9][N:10]2[CH2:14][CH2:13][N:12]([C:15]3[S:16][C:17]([C:21]([NH:59][CH2:60][C:61]4[CH:62]=[N:63][CH:64]=[CH:65][CH:66]=4)=[O:23])=[C:18]([CH3:20])[N:19]=3)[C:11]2=[O:24])=[CH:26][CH:27]=1

Participants

8

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 579197422-(3-(2-(4-Fluorobenzylamino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 579197492-(3-(2-(4-fluorobenzylamino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)-4-methyl-N-(pyridin-3-ylmethyl)thiazole-5-carboxamideYield 28%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of crude 2-(3-(2-(4-fluorobenzylamino)-2-oxoethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid (0.18 g, 0.46 mmol), 1-hydroxybenzotriazole (0.09 g, 0.69 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.13 g, 0.69 mmol) in N,N-dimethylformamide (2 mL) was added N,N-diisopropylethylamine (0.24 mL, 1.38 mmol) and 3-(aminomethyl)pyridine (0.05 mL, 0.46 mmol). The resulting reaction mixture was stirred for 18 h and diluted with ethyl acetate (75 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution (2×35 mL) and water (35 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 5-15% methanol in dichloromethane to afford the title compound as a colorless foamy solid (0.06 g, 28%): 1H NMR (300 MHz, CDCl3) δ 8.57-8.54 (m, 1H), 8.51-8.47 (m, 1H), 7.71-7.65 (m, 1H), 7.30-7.22 (m, 3H), 6.97-6.90 (m, 2H), 6.43 (br s, 1H), 6.05 (t, J=5.8 Hz, 1H), 4.55 (d, J=5.8 Hz, 2H), 4.51 (s, 2H), 4.01 (s, 2H), 3.63-3.53 (m, 4H), 2.39 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 169.5, 167.7, 162.4, 160.7, 157.1, 154.2, 149.1, 148.8, 135.7, 134.1, 131.6 (d, JC-F=3.2 Hz), 130.4 (d, JC-F=8.2 Hz), 123.6, 115.5 (d, JC-F=21.5 Hz), 113.2, 50.3, 42.9, 42.6, 41.8, 41.3, 17.5; MS (ES+) m/z 483.2 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution (2×35 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 5-15% methanol in dichloromethane

Sources & evidence

ORD record
ord-4182bbafcba94e7b90bff4d99944cdaf
Source dataset
uspto-grants-2011_11
Patent number
US08049016B2

Reaction notes

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