4-Fluorobenzylamine → 2-(3-benzyl-2-oxoimidazolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

HRID 2067405Notes

Reaction equation

HRID 2067405 reaction equation
[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C:13]2[S:14][C:15]([C:19]([OH:21])=O)=[C:16]([CH3:18])[N:17]=2)[C:9]1=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.[F:54][C:55]1[CH:62]=[CH:61][C:58]([CH2:59][NH2:60])=[CH:57][CH:56]=1>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C:13]2[S:14][C:15]([C:19]([NH:60][CH2:59][C:58]3[CH:61]=[CH:62][C:55]([F:54])=[CH:56][CH:57]=3)=[O:21])=[C:16]([CH3:18])[N:17]=2)[C:9]1=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 673264-FluorobenzylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 579198662-(3-Benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid

Product 1

HCID 250945992-(3-benzyl-2-oxoimidazolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamideYield 58%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid (0.32 g, 1.00 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.20 g, 1.30 mmol) and N,N-diisopropylethylamine (0.50 mL, 2.80 mmol) in N,N-dimethylformamide (20 mL) was added 1-hydroxybenzotriazole (0.16 g, 1.20 mmol). The resulting mixture was stirred at ambient temperature for 15 minutes and 4-fluorobenzylamine (0.17 mL, 1.45 mmol) was added. The reaction mixture was kept stirring for 27 hours at ambient temperature, then was diluted with ethyl acetate (300 mL) and washed with water and brine. The organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography to afford the title compound as a white powder in 58% yield (0.25 g): mp 147-148° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.35-7.20 (m, 7H), 7.02-6.96 (m, 2H), 6.00 (s, 1H), 4.55-4.44 (m, 4H), 4.04 (t, J=7.5 Hz, 2H), 3.42 (t, J=7.5 Hz, 2H), 2.59 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 163.8, 162.4, 160.5, 157.3, 155.3, 153.2, 135.5, 133.8, 129.4, 128.9, 128.2, 117.0, 115.7, 47.9, 43.2, 42.0, 41.6, 17.1; MS (ES+) m/z 425.2 (M+1).

Workup

  1. stirringThe reaction mixture was kept stirring for 27 hours at ambient temperature
  2. washwashed with water and brine
  3. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-f099b11fac674723b8acf6cd9c884a69
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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