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

HRID 472934Notes

Reaction equation

HRID 472934 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>[C:22]([C:27]1[N:8]([CH2:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[C:7]2[CH:6]=[CH:5][C:4]([NH:16][C:17](=[O:20])[O:18][CH3:19])=[CH:3][C:2]=2[N:1]=1)([CH3:26])([CH3:23])[CH3:21]

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 in dropwise and the solution was stirred at rt for 1 h. The solvent was concentrated. The residue was divided in two portions and each of them was 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 contents of the two tubes were combined and the solvent was evaporated. The residue was dissolved in EtOAc and washed with saturated NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by flash chromatography using 3:1/dichloromethane:diethyl ether. Yield: 656 mg (56%); 1H NMR (400 MHz, CHLOROFORM-D) δ 1.08 (m, 2H), 1.18 (m, 3H), 1.54 (s, 9H), 1.65 (m, 1H), 1.69 (m, 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 was 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 solution, brine
  8. dry with materialdried over anhydrous MgSO4
  9. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-b925916c1c504f9d80fa9f4c91e3e3cf
Source dataset
uspto-grants-2014_01
Patent number
US08633235B2

Reaction notes

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