Potassium Carbonate → N-benzyl-4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxamide

HRID 2067549Notes

Reaction equation

HRID 2067549 reaction equation
[NH2:1][C:2]1[S:3][C:4]([C:8]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])=[C:5]([CH3:7])[N:6]=1.C(N(CC)C(C)C)(C)C.Cl[CH2:28][CH2:29][N:30]=[C:31]=[O:32].C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[CH2:11]([NH:10][C:8]([C:4]1[S:3][C:2]([N:1]2[CH2:28][CH2:29][NH:30][C:31]2=[O:32])=[N:6][C:5]=1[CH3:7])=[O:9])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 160352-Chloroethyl isocyanateHCID 81531DiisopropylethylamineHCID 210824N-Benzyl-2-imino-4-methyl-2,3-dihydro-1,3-thiazole-5-carboximidic acid

Product 1

HCID 59481185N-benzyl-4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxamideYield 60%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-amino-N-benzyl-4-methylthiazole-5-carboxamide (3.00 g, 12.1 mmol) in tetrahydrofuran (70 mL) was added N,N-diisopropylethylamine (3.13 g, 24.3 mmol), followed by the addition of 2-chloroethyl isocyanate (1.66 g, 15.76 mmol) at ambient temperature. The resulting reaction mixture was stirred at ambient temperature for 2 days. The solvent was removed in vacuo and the residue was washed with water (100 mL) and t-butyl methyl ether (200 mL). The resulting white solid was added to a suspension of potassium carbonate (2.01 g, 14.55 mmol) and tetrabutylammonium iodide (0.16 g, 0.44 mmol) in dioxane (50 mL). The reaction mixture was refluxed for 24 hours. The solvent was removed in vacuo, and the residue was washed with water (200 mL) and ethyl acetate (50 mL). The residue was recrystallized in methanol to afford the title compound as a colorless solid in 60% yield (2.3 g): mp 226-228° C. (methanol); 1H NMR (300 MHz, DMSO-d6) δ 8.45 (t, J=5.8 Hz, 1H), 7.71 (s, 1H), 7.31-7.16 (m, 5H), 4.33 (d, J=5.8 Hz, 2H), 3.99 (m, 2H), 3.46 (m, 2H), 2.43 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.2, 157.6, 157.1, 151.4, 140.1, 128.6, 127.6, 127.1, 118.1, 44.5, 43.0, 37.7, 17.5; MS (ES+) m/z 317.2 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. customThe solvent was removed in vacuo
  3. washthe residue was washed with water (100 mL) and t-butyl methyl ether (200 mL)
  4. temperatureThe reaction mixture was refluxed for 24 hours
  5. customThe solvent was removed in vacuo
  6. washthe residue was washed with water (200 mL) and ethyl acetate (50 mL)
  7. customThe residue was recrystallized in methanol

Sources & evidence

ORD record
ord-432524b42e1a4bbca57f4be6af18d261
Source dataset
uspto-grants-2012_10
Patent number
US08293768B2

Reaction notes

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