Cesium carbonate → 1-({4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]cyclohex-3-en-1-yl}methyl)-3-methylimidazolidine-2,4-dione

HRID 1626985Notes

Reaction equation

HRID 1626985 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH2:20][CH2:19][CH:18]([CH2:21]I)[CH2:17][CH:16]=1.[CH3:23][N:24]1[C:28](=[O:29])[CH2:27][NH:26][C:25]1=[O:30].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].C(=O)(O)[O-].[Na+]>C(#N)C>[Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:15]1[CH2:20][CH2:19][CH:18]([CH2:21][N:26]2[CH2:27][C:28](=[O:29])[N:24]([CH3:23])[C:25]2=[O:30])[CH2:17][CH:16]=1

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 1388512,4-Imidazolidinedione, 3-methyl-2×HCID 516892Sodium BicarbonateHCID 867137494-Chloro-1-(cyclopropylmethyl)-5-[4-(iodomethyl)cyclohex-1-en-1-yl]-1H-benzotriazole

Product 1

HCID 709780491-({4-[4-chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]cyclohex-3-en-1-yl}methyl)-3-methylimidazolidine-2,4-dione

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

4-Chloro-1-(cyclopropylmethyl)-5-[4-(iodomethyl)cyclohex-1-en-1-yl]-1H-benzotriazole (0.12 g, 0.29 mmol), 3-methylimidazolidine-2,4-dione (67 mg, 0.58 mmol, 2 equiv) and potassium carbonate (0.20 g, 1.5 mmol, 5 equiv) were combined in acetonitrile (5 mL) and placed into a preheated oil bath at 85° C. for 3 hours. Additional 3-methylimidazolidine-2,4-dione (0.13 mg, 1.2 mmol, 4 equiv) and cesium carbonate (0.48 g, 1.5 mmol, 5 equiv) were added and the mixture was heated at 85° C. for an additional 45 minutes. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (50 mL, aqueous saturated) and extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate), providing the titled compound as a colorless foam: 1H-NMR (400 MHz, CDCl3) δ 7.41 (1H, d, J=8.5 Hz), 7.30 (1H, d, J=8.5 Hz), 5.77-5.72 (1H, m), 4.51 (2H, d, J=7.1 Hz), 3.94 (2H, s), 3.47 (1H, dd, J=14.0, 7.4 Hz), 3.40 (1H, dd, J=14.0, 7.2 Hz), 3.05 (3H, s), 2.53-2.38 (2H, m), 2.33 (1H, br d, J=17.7 Hz), 2.15-1.87 (3H, m), 1.61-1.51 (1H, m), 1.45-1.34 (1H, m), 0.69-0.64 (2H, m), 0.51-0.47 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 414.1702 [(M+H)+; calculated for C21H25ClN5O2: 414.1691].

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionextracted with ethyl acetate (2×75 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-0c9b612afc7146d9a58cbfcf24defa8a
Source dataset
uspto-grants-2014_07
Patent number
US08785482B2

Reaction notes

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