Pivaloyl chloride → Methyl [2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]carbamate

HRID 1783891Notes

Reaction equation

HRID 1783891 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:16][C:17](=[O:20])[O:18][CH3:19])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.[CH3:21][C:22]([CH3:27])([CH3:26])[C:23](Cl)=O>CN(C1C=CN=CC=1)C.ClCCl>[CH3:19][O:18][C:17](=[O:20])[NH:16][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([CH2:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[C:21]([C:22]([CH3:27])([CH3:26])[CH3:23])=[N:1][C:2]=2[CH:3]=1

Participants

5

Reactant 2

HCID 62493Pivaloyl chlorideHCID 57591006Methyl {3-amino-4-[(cyclohexylmethyl)amino]phenyl}carbamate

Product 1

HCID 11588208Methyl [2-tert-butyl-1-(cyclohexylmethyl)-1H-benzimidazol-5-yl]carbamate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Methyl {3-amino-4-[(cyclohexylmethyl)amino]phenyl}carbamate (950 mg, 3.43 mmol) and DMAP (100 mg, 0.858 mmol) were dissolved in 25 mL of dichloromethane. Trimethylacetyl chloride (0.460 mL, 3.77 mmol) was added dropwise and the solution stirred at RT for 1 h. The solvent was concentrated. The residue was divided in two and each of them dissolved in 3 mL of glacial AcOH in a sealed tube. The solutions were heated at 150° C. using a Personal Chemistry Smith Synthesizer microwave instrument for three intervals of 30 min (3×30 min). The two tubes were combined and the solvent was evaporated. The residue was dissolved in EtOAc and washed with saturated NaHCO3 aqueous solution, brine and dried over anhydrous MgSO4. The crude product was purified by flash chromatography using 3:1/dichloromethane:diethyl ether on silica gel. Yield: 656 mg (56%); 1H NMR (400 MHz, CHLOROFORM-D) δ 1.09 (m, 2H), 1.16 (m, 4H), 1.54 (s, 9H), 1.65 (m, 1H), 1.62 (m, 1H), 1.70 (m, J=1.56 Hz, 2H), 1.73 (dd, J=5.96, 3.22 Hz, 2H), 2.02 (m, 1H), 3.78 (s, 3H), 4.10 (d, J=7.42 Hz, 2H), 6.64 (m, 1H), 7.25 (d, J=8.79 Hz, 1H), 7.39 (m, 1H), 7.59 (d, J=1.76 Hz, 1H).

Workup

  1. concentrationThe solvent was concentrated
  2. dissolutioneach of them dissolved in 3 mL of glacial AcOH in a sealed tube
  3. temperatureThe solutions were heated at 150° C.
  4. customfor three intervals of 30 min (3×30 min)
  5. customthe solvent was evaporated
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with saturated NaHCO3 aqueous solution, brine
  8. dry with materialdried over anhydrous MgSO4
  9. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-a8d54946ad3147e7b2825390666925f5
Source dataset
uspto-grants-2009_03
Patent number
US07501447B2

Reaction notes

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