4-Toluenesulfonyl chloride → HCID 22100726, compound

HRID 1458420Notes

Reaction equation

HRID 1458420 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:23]=[CH:22][C:18]3[N:19]=[CH:20][NH:21][C:17]=3[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[S:26](Cl)([C:29]1[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=1)(=[O:28])=[O:27].C(OCC)(=O)C>CN(C=O)C.O>[S:26]([N:19]1[C:18]2[CH:22]=[CH:23][C:15]([NH:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)=[CH:16][C:17]=2[N:21]=[CH:20]1)([C:29]1[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=1)(=[O:28])=[O:27].[S:26]([N:21]1[C:17]2[CH:16]=[C:15]([NH:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]3)[CH:23]=[CH:22][C:18]=2[N:19]=[CH:20]1)([C:29]1[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=1)(=[O:28])=[O:27]

Participants

8

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 22100837HCID 22100837, compound

Product 2

HCID 22100726HCID 22100726, compoundHCID 22100825HCID 22100825, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-((N-(tert-butoxycarbonyl)piperidin-4-yl)amino)benzimidazole (1.50 g, 4.75 mmol) in DMF (30 mL) at 0° C. was added NaH (210 mg, 5.2 mmol). The solution was stirred for 0.5 hours when tosyl chloride (1.0 g, 5.2 mmol) was added. The reaction mixture was stirred for 1 hour at 0° C. when it was worked up with ethyl acetate and water, dried (MgSO4), and concentrated to an oil to afford 1-tosyl-5-((N-(tert-butoxycarbonyl)piperidin-4-yl)amino)benzimidazole and its regioisomer, 1-tosyl-6-((N-(tert-butoxycarbonyl)piperidin-4-yl)amino)benzimidazole. The resulting oil was taken up in DMF (30 mL) when it was charged with K2CO3 (4 g) and methyl iodide (3 mL). After 12 hours at ambient temperature, the reaction mixture was worked up with ethyl acetate and water, dried (MgSO4), and concentrated to an oil. The resulting tosylated product, 1-tosyl-5-((N-(tert-butoxycarbonyl)piperidin-4-yl)(methyl)amino)benzimidazole and the corresponding regioisomer, was taken up in methanol (80 mL) and NaOH (0.3 g, 7.5 mmol) was added. After 1 hour at ambient temperature, the methanol was removed in vacuo and the product recovered via chromatography on silica gel eluting with 5% to 10% methanol in methylene chloride to give 473 mg (30%) 5-((N-(tert-butoxycarbonyl)piperidin-4-yl)(methyl)amino)benzimidazole.

Workup

  1. additionwas added
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated to an oil

Sources & evidence

ORD record
ord-0190189e58654d4db399b12a44ab7d30
Source dataset
uspto-grants-1998_12
Patent number
US05849759

Reaction notes

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