Ammonia → 1-(Cyclopropylmethyl)-2-(2,2-dimethylpropyl)-5-(isopropylsulfonyl)-1H-benzimidazole

HRID 1817851Notes

Reaction equation

HRID 1817851 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([S:8]([CH:11]([CH3:13])[CH3:12])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:14][CH2:15][CH:16]1[CH2:18][CH2:17]1.[C:19]([CH2:23][C:24](Cl)=O)([CH3:22])([CH3:21])[CH3:20].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.N>C(OCC)(=O)C.O>[CH:16]1([CH2:15][N:14]2[C:3]3[CH:4]=[CH:5][C:6]([S:8]([CH:11]([CH3:13])[CH3:12])(=[O:9])=[O:10])=[CH:7][C:2]=3[N:1]=[C:24]2[CH2:23][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 815143,3-Dimethylbutanoyl chlorideHCID 521998p-Toluenesulfonic acid monohydrateHCID 688699912-Amino-1-(N-cyclopropylmethylamino)-4-(isopropylsulfonyl)benzene

Product 1

HCID 116602881-(Cyclopropylmethyl)-2-(2,2-dimethylpropyl)-5-(isopropylsulfonyl)-1H-benzimidazoleYield 55.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-amino-1-(N-cyclopropylmethylamino)-4-(isopropylsulfonyl)benzene (Step E, 113 mg, 0.38 mmol) in ethyl acetate (3 mL) was added tert-butylacetyl chloride (58 μL, 0.42 mmol) at room temperature. After stirring for 1 h, p-toluenesulfonic acid monohydrate (72 mg, 0.38 mmol) was added and the mixture was stirred under reflux for 3 h. Water (5 mL) and aqueous ammonia (0.5 mL) were added and the mixture was extracted with ethyl acetate (15 mL×3) and washed with brine (5 mL). The organic extracts were dried over sodium sulfate and concentrated. The residue was purified by pTLC (hexane:ethyl acetate=1:1 then dichloromethane:methanol=10:1 as eluent) to give colorless oil (74 mg), which was recrystalized from ethyl acetate and hexane to afford the title compound (28 mg, 21%) as a white solid.

Workup

  1. stirringthe mixture was stirred
  2. temperatureunder reflux for 3 h
  3. extractionthe mixture was extracted with ethyl acetate (15 mL×3)
  4. washwashed with brine (5 mL)
  5. dry with materialThe organic extracts were dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by pTLC (hexane

Sources & evidence

ORD record
ord-755637ec0bd242f29384ed17a27ffe6e
Source dataset
uspto-grants-2009_10
Patent number
US07598393B2

Reaction notes

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