ethyl 4,4,4-triethoxybutanoate

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-1-(2-(3-ethylureido)benzo[b]thiophene-3-carbonyl)piperidine-4-carboxamide (7, 100 mg, 1.0 equivalent) as prepared in Example 7 was dissolved in toluene (0.09 M) and DMF (0.26 M), and to which acetic acid (2.0 equivalents), and ethyl 4,4,4-triethoxybutanoate (4.0 equivalents) were added and the reaction mixture was heated to 85° C. for 9 hrs. The reaction mixture was then partitioned between ethyl acetate and water and the separated organics was washed with brine and dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by SiO2 chromatography (5%-10% MeOH/CH2Cl2 gradient) to afford ethyl 3-(8-(2-(3-ethylureido)benzo[b]thiophene-3-carbonyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-2-yl)propanoate (10, 65%). Two rotamers observed (ratio 1.3:1). The reaction mixture was then partitioned between ethyl acetate and water the separated organics was washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The residue was purified by SiO2 chromatography (5%-10% MeOH/CH2Cl2 gradient)

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Amino-1-(2-(3-ethylureido)benzo[b]thiophene-3-carbonyl)piperidine-4-carboxamide (7, 100 mg, 1.0 equivalent) as prepared in Example 7 was dissolved in toluene (0.09 M) and DMF (0.26 M), and to which acetic acid (2.0 equivalents), and ethyl 4,4,4-triethoxybutanoate (4.0 equivalents) were added and the reaction mixture was heated to 85° C. for 9 hrs. The reaction mixture was then partitioned between ethyl acetate and water and the separated organics was washed with brine and dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by SiO2 chromatography (5%-10% MeOH/CH2Cl2 gradient) to afford ethyl 3-(8-(2-(3-ethylureido)benzo[b]thiophene-3-carbonyl)-4-oxo-1,3,8-triazaspiro[4.5]dec-1-en-2-yl)propanoate (10, 65%). Two rotamers observed (ratio 1.3:1). The reaction mixture was then partitioned between ethyl acetate and water the separated organics was washed with brine dried over Na2SO4 filtered concentrated under reduced pressure The residue was purified by SiO2 chromatography (5%-10% MeOH/CH2Cl2 gradient)