Reaction #43767

ord-554b8d9aa4d54e20948efc4898a43dec

Reaction equation

Cl.N#Cc1cccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc12
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-cyano-1-benzo-thiophene-2-carboxamide hydrochloride
Cl.NO
hydroxylamine hydrochloride
O=C([O-])[O-].[K+].[K+]
potassium carbonate
O
water
→
Cl.Cl.N/C(=N\O)c1cccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc12
title compound
Cl.Cl.N/C(=N\O)c1cccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc12
7-[(Z)-Amino(hydroxyimino)methyl]-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzo-thiophene-2-carboxamide dihydrochloride

Reactants

Cl.N#Cc1cccc2cc(C(=O)N[C@H]3CN4CCC3CC4)sc12
N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-cyano-1-benzo-thiophene-2-carboxamide hydrochloride
Cl.NO
hydroxylamine hydrochloride
O=C([O-])[O-].[K+].[K+]
potassium carbonate
O
water

Reagents

None

Solvents

CCO
ethanol

Conditions

Temperature
80°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    OtherThe mixture is purified by preparative HPLC
  2. 2
    Concentrationconcentrated
  3. 3
    workup.ADDITIONacetonitrile and 1N aqueous hydrochloric acid (3:1) are added
  4. 4
    Concentrationthe mixture is then again concentrated
  5. 5
    Otherdried under high vacuum

Procedure

120 mg (0.43 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-cyano-1-benzo-thiophene-2-carboxamide hydrochloride, 45.0 mg (0.65 mmol) of hydroxylamine hydrochloride and 119.2 mg (0.86 mmol) of potassium carbonate in 1.5 ml of an 8:1 mixture of water and ethanol are heated at 80° C. for 18 h. The mixture is purified by preparative HPLC. The product fractions are combined and concentrated, acetonitrile and 1N aqueous hydrochloric acid (3:1) are added and the mixture is then again concentrated and dried under high vacuum. 58 mg (30.3% of theory) of the title compound are obtained.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07732477B2uspto-grants-2010_06