Hydrochloric Acid → 1-Isopropylsulfonyl-2-amino-6-(alpha-hydroxy-alpha-aminocarbonylmethylbenzyl)benzimidazole

HRID 904828Notes

Reaction equation

HRID 904828 reaction equation
C[Si]([CH:5]([Si](C)(C)C)[C:6]([NH2:8])=[O:7])(C)C.C([Li])CCC.[CH:18]([S:21]([N:24]1[C:28]2[CH:29]=[C:30]([C:33](=[O:40])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:31]=[CH:32][C:27]=2[N:26]=[C:25]1[NH2:41])(=[O:23])=[O:22])([CH3:20])[CH3:19].C(C1NC2C=CC=CC=2N=1)(=O)C1C=CC=CC=1.Cl>O.O1CCCC1>[CH:18]([S:21]([N:24]1[C:28]2[CH:29]=[C:30]([C:33]([OH:40])([CH2:5][C:6]([NH2:8])=[O:7])[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH:31]=[CH:32][C:27]=2[N:26]=[C:25]1[NH2:41])(=[O:22])=[O:23])([CH3:20])[CH3:19]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3035251H-benzimidazol-2-yl(phenyl)methanoneHCID 30173892-Amino-6-benzoyl-1-((isopropyl)sulphonyl)-1H-benzimidazoleHCID 11708267BistrimethylsilylacetamidHCID 178418339Butyllithium

Product 1

HCID 204777191-Isopropylsulfonyl-2-amino-6-(alpha-hydroxy-alpha-aminocarbonylmethylbenzyl)benzimidazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 50 ml. of tetrahydrofuran containing 7.33 ml. of bistrimethylsilylacetamide (30 millimoles) and 18.75 ml. of a 1.6 Molar solution of n-butyl lithium (30 millimoles) was stirred at -78° C. for ten minutes. A solution of 1.03 g. (3 millimoles) of 1-isopropylsulfonyl-2-amino-6-benzoylbenzimidazole in 100 ml. of tetrahydrofuran was then added to the cold reaction mixture dropwise over one hour. The temperature of the reaction mixture was maintained at -78° C. throughout the addition, and the reaction mixture was stirred for four hours at -78° C. following complete addition of the benzoylbenzimidazole. The reaction mixture next was diluted with 75 ml. of water and 33 ml. of 1 N hydrochloric acid. The organic layer was separated and the aqueous acid layer was extracted several times with ethyl acetate. The organic layer and extracts were combined, washed with fresh water and dried. Removal of the solvent by evaporation under reduced pressure afforded a white solid product. Purification of the product by chromatography over silica gel afforded 1-isopropylsulfonyl-2-amino-6-(α-hydroxy-α-aminocarbonylmethylbenzyl)benzimidazole.

Workup

  1. additionThe reaction mixture next was diluted with 75 ml
  2. customThe organic layer was separated
  3. extractionthe aqueous acid layer was extracted several times with ethyl acetate
  4. washwashed with fresh water
  5. customdried
  6. customRemoval of the solvent
  7. customby evaporation under reduced pressure
  8. customafforded a white solid product
  9. customPurification of the product by chromatography over silica gel

Sources & evidence

ORD record
ord-85a42f19faae4405a93754cb09915f67
Source dataset
uspto-grants-1983_12
Patent number
US04420479

Reaction notes

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