Acetic Acid → N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-amino-1-benzothiophene-2-carboxamide dihydrochloride

HRID 658205

Reaction equation

HRID 658205 reaction equation
[ClH:1].[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2.C(O)(=O)C>[Zn].O>[ClH:1].[ClH:1].[N:2]12[CH2:7][CH2:6][CH:5]([CH2:8][CH2:9]1)[C@@H:4]([NH:10][C:11]([C:13]1[S:14][C:15]3[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:16]=3[CH:17]=1)=[O:12])[CH2:3]2

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 68429753N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-nitro-1-benzothiophene-2-carboxamide hydrochloride

Product 1

HCID 68431067N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5-amino-1-benzothiophene-2-carboxamide dihydrochloride

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 962WaterSolvent

Procedure

385.0 mg (1.05 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-5-nitro-1-benzothiophene-2-carboxamide hydrochloride are suspended in 10 ml of a 1:1 mixture of acetic acid and water. 300.0 mg (4.59 mmol) of zinc are added, and the mixture is then stirred at RT for 1 h. The reaction mixture is filtered through kieselguhr, and the filter cake is washed with methanol. The filtrate is concentrated under reduced pressure and the residue is purified by preparative HPLC. The product fraction is dissolved in 4M HCl in dioxane, concentrated under reduced pressure and recrystallized from acetonitrile. 233 mg (59.5% of theory) of the title compound are obtained.

Workup

  1. filtrationThe reaction mixture is filtered through kieselguhr
  2. washthe filter cake is washed with methanol
  3. concentrationThe filtrate is concentrated under reduced pressure
  4. customthe residue is purified by preparative HPLC
  5. dissolutionThe product fraction is dissolved in 4M HCl in dioxane
  6. concentrationconcentrated under reduced pressure
  7. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-206fdec4438544ad945f21d6d6a81be4
Source dataset
uspto-grants-2011_12
Patent number
US08076355B2

Linked notes

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