Dimethylsulphamoyl chloride → HCID 11154007, compound

HRID 472936Notes

Reaction equation

HRID 472936 reaction equation
[CH:1]1([CH2:7][N:8]2[C:12]3[CH:13]=[CH:14][C:15]([NH2:17])=[CH:16][C:11]=3[N:10]=[C:9]2[C:18]([CH3:22])([CH3:21])[CH2:19][CH3:20])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:23][N:24]([CH3:29])[S:25](Cl)(=[O:27])=[O:26]>CN(C1C=CN=CC=1)C.C(#N)C>[CH:1]1([CH2:7][N:8]2[C:12]3[CH:13]=[CH:14][C:15]([NH:17][S:25]([N:24]([CH3:29])[CH3:23])(=[O:27])=[O:26])=[CH:16][C:11]=3[N:10]=[C:9]2[C:18]([CH3:21])([CH3:22])[CH2:19][CH3:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 83372Dimethylsulphamoyl chlorideHCID 57591002HCID 57591002, compound

Product 1

HCID 11154007HCID 11154007, compoundYield 76.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

DMAP (80.1 mg, 0.65 mmol) was added to a solution of 1-(cyclohexylmethyl)-2-(1,1-dimethylpropyl)-1H-benzimidazol-5-amine (69.5 mg, 0.18 mmol) (for preparation, see the following steps B, C, D, E and F) in acetonitrile (10 mL) at 0° C., followed by addition of dimethylsulfamoyl chloride (22 uL, 28.7 mg, 0.20 mmol). The resulting mixture was heated at reflux for 20 h and then quenched with MeOH (2 mL). After evaporation of the solvent, the residue was dissolved in EtOAc (100 mL) and washed with NaCl aqueous solution (10 mL) and dried over Na2SO4. After filtration and evaporation, the residue was purified by MPLC (hexanes/EtOAc 1:1 as eluent on silica gel) to give the title compound as a white solid (56.2 mg, 76%), which was converted to a white solid as a TFA salt. 1H NMR (400 MHz, CD3OD): δ 0.84 (t, J=7.52 Hz, 3H), 1.24 (m, 5H), 1.64 (m, 2H), 1.66 (s, 6 μl), 1.71 (m, 1H), 1.78 (m, 2H), 2.01 (q, J=7.55 Hz, 2H), 2.11 (m, 1H), 2.82 (s, 6H), 4.44 (d, J=7.81 Hz, 2H), 7.37 (dd, J=8.98, 2.15 Hz, 1H), 7.69 (d, J=2.15 Hz, 1H), 7.84 (d, J=8.98 Hz, 1H); MS (ESI) (M+H)+: 407.3; Anal. Calcd for C21H34N4O2S+1.0 TFA+0.2 H2O: C, 52.70; H, 6.81; N, 10.69. Found: C, 52.70; H, 6.66; N, 10.45.

Workup

  1. customfor preparation
  2. customat 0° C.
  3. temperatureThe resulting mixture was heated
  4. temperatureat reflux for 20 h
  5. customquenched with MeOH (2 mL)
  6. customAfter evaporation of the solvent
  7. dissolutionthe residue was dissolved in EtOAc (100 mL)
  8. washwashed with NaCl aqueous solution (10 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationAfter filtration and evaporation
  11. customthe residue was purified by MPLC (hexanes/EtOAc 1:1 as eluent on silica gel)

Sources & evidence

ORD record
ord-56c04172abde4a47b4a5e0f344921740
Source dataset
uspto-grants-2014_01
Patent number
US08633235B2

Reaction notes

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