Methyl iodide → HCID 70978779, compound

HRID 2281078Notes

Reaction equation

HRID 2281078 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[CH:28]=[CH:27][C:18]([CH2:19][N:20]2[C:24](=[O:25])[CH2:23][NH:22][C:21]2=[O:26])=[CH:17][CH:16]=1.[C:29](=O)([O-])[O-].[K+].[K+].IC>CN(C)C=O.C(OCC)(=O)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[CH:16]=[CH:17][C:18]([CH2:19][N:20]2[C:24](=[O:25])[CH2:23][N:22]([CH3:29])[C:21]2=[O:26])=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 11430Potassium Carbonate2×HCID 70978474HCID 70978474, compound

Product 1

HCID 70978779HCID 70978779, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-{4-[4-Chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl]benzyl}imidazolidine-2,4-dione (Example 84, 19 mg, 0.048 mmol) was dissolved in N,N-dimethylformamide and treated with potassium carbonate (8.6 mg, 0.062 mmol, 1.3 equiv) and iodomethane (5.4 μL, 0.086 mmol, 1.8 equiv). After stirring at ambient temperature for 1 hour, additional iodomethane (5.4 μL, 0.086 mmol, 1.8 equiv) and potassium carbonate (8.6 mg, 0.062 mmol, 1.3 equiv) were added and the mixture was placed into a preheated oil bath at 50° C. for 2.5 hours. The mixture was cooled to ambient temperature, diluted with ethyl acetate (30 mL) and washed with sodium bicarbonate (2×20 mL, aqueous saturated). The organic extract was dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative reverse phase HPLC (85:15 to 36:64; water with 0.05% trifluoroacetic acid:acetonitrile with 0.05% trifluoroacetic acid) to afford the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 7.53 (1H, d, J=6.5 Hz); 7.51 (2H, d, J=6.7 Hz); 7.48 (2H, d, J=2.7 Hz); 7.45 (1H, d, J=2.9 Hz); 4.73 (2H, s); 4.55 (2H, d, J=7.2 Hz); 3.92 (2H, s); 3.02 (3H, s); 1.47-1.39 (1H, m); 0.72-0.67 (2H, m); 0.54-0.50 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 410.1380 [(M+H)+; calculated for C21H21ClN5O2: 410.1378].

Workup

  1. waitthe mixture was placed into a preheated oil bath at 50° C. for 2.5 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. washwashed with sodium bicarbonate (2×20 mL, aqueous saturated)
  4. extractionThe organic extract
  5. dry with materialwas dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative reverse phase HPLC (85:15 to 36:64; water with 0.05% trifluoroacetic acid:acetonitrile with 0.05% trifluoroacetic acid)

Sources & evidence

ORD record
ord-3541a791972749089b74da20b885be61
Source dataset
uspto-grants-2015_09
Patent number
US09139576B2

Reaction notes

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