Water → HCID 67313737, compound

Participants

Reaction Steps

110 mg (0.26 mmol) of 6-[amino(hydroxyimino)methyl]-N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-1-benzothiophene-2-carboxamide dihydrochloride (Example 27A) are dissolved in 2 ml of DMF and 0.75 ml of THF. 250 mg of 4 Å molecular sieves are added and the mixture is stirred at room temperature for 30 min. Addition of 31.2 mg (0.79 mmol) of sodium hydride (60% suspension in mineral oil) is followed by heating at 60° C. for 20 min and then cooling to room temperature. A solution of 100 μl (0.79 mmol) of methyl benzoate in 1 ml of THF is added to the reaction mixture, and it is heated at 80° C. for 14 h. A further 20.8 mg (0.52 mmol) of sodium hydride (60% suspension in mineral oil) and 0.99 ml (7.91 mmol) of methyl benzoate in 1 ml of THF are added, and the mixture is heated at 70° C. for a further 24 h. The reaction is stopped by adding water. Purification takes place by preparative HPLC. The product fractions are concentrated and, after addition of a 5:1 mixture of methanol and 4N hydrogen chloride in dioxane, again concentrated. Drying under high vacuum results in 45.7 mg (32% of theory) of the title compound.

Provenance & Evidence