2-ethoxyaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: The title compound was synthesized according to the procedure described for the preparation of Example 188 using Compound 83 (100 mg, 0.43 mmol) and 2-ethoxyaniline (119 mg, 0.87 mmol) to provide 198 (123 mg, 86% yield) as a white solid. LC-MS (M+H=332, obsd.=332). The title compound was synthesized

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

Procedure: Ethyl 1,6-dihydro-2-methylthio-6-oxo-5-pyrimidinecarboxylate (8 g) and 2-ethoxyaniline (6.1 g) are added to ethanol (60 ml), and the mixture is refluxed with stirring for 48 hours. After cooling, the precipitate is collected by filtration, washed with ethanol and recrystallized from a mixture of DMF and water to give ethyl 1,6-dihydro-2-(2-ethoxyanilino)-6-oxo-5-pyrimidinecarboxylate (7.5 g). M.p. 220°-221° C. the mixture is refluxed After cooling the precipitate is collected by filtration washed with ethanol recrystallized from a mixture of DMF and water

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

Procedure: Ethyl 1,6-dihydro-2-methylthio-6-oxo-5-pyrimidinecarboxylate (8 g) and 2-ethoxyaniline (6.1 g) are added to ethanol (60 ml), and the mixture is refluxed with stirring for 48 hours. After cooling, the precipitate is collected by filtration, washed with ethanol and recrystallized from a mixture of DMF and water to give ethyl 1,6-dihydro-2-(2-ethoxyanilino)-6-oxo-5-pyrimidinecarboxylate (7.5 g). M.p. 220°-221° C. the mixture is refluxed After cooling the precipitate is collected by filtration washed with ethanol recrystallized from a mixture of DMF and water

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-ethoxyaniline (54.8 g.), methanol (300 ml.) and epichlorhydrin (18.6 g.) is stirred at 25° C. for 24 hours. The methanol and unreacted 2-ethoxyaniline are removed by vacuum distillation and the residue is dissolved in methanol (300 ml.) and sodium hydroxide (8.0 g.) added. The mixture is stirred at 25° C. for 3 hours, filtered and the filtrate evaporated under reduced pressure to give N-glycidyl-2-ethoxyaniline which is then dissolved in methanol (69 ml.). This solution is added to a stirred suspension of 2-aminoethyl hydrogen sulphate (97.0 g.) in a mixture of methanol (69 ml.), water (16.5 ml.) and sodium hydroxide solution (17 N; 35.0 ml.). The mixture is stirred at 25° C. for 16 hours. The methanol and unreacted 2-ethoxyaniline are removed by vacuum distillation the residue is dissolved in methanol (300 ml.) sodium hydroxide (8.0 g.) added The mixture is stirred at 25° C. for 3 hours filtered the filtrate evaporated under reduced pressure

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-ethoxyaniline (14.0 g.) and 4-benzyl-2-toluene-p-sulphonyloxymethylmorpholine (18.6 g.) is stirred and heated on the steam bath (95° C.) under nitrogen for 24 hours. The mixture is cooled and ether added. The solid thus obtained is collected and crystallised from ethyl acetate to give 4-benzyl-2-(2-ethoxyanilino)methylmorpholine toluene-p-sulphonate, m.p. 127° C. The toluene sulphonate salt is converted into the corresponding dihydrochloride by basifying it with dilute sodium hydroxide solution, extracting the base into ether (3× 200 ml.), washing the ethereal extract with water and then drying it over anhydrous magnesium sulphate followed by filtration and treatment of the ethereal solution of base with ethereal hydrochloric acid solution. The 4-benzyl-2-(2-ethoxyanilino)-methylmorpholine dihydrochloride melts at 226° C. after crystallisation from methanol/ethyl acetate. The mixture is cooled The solid thus obtained is collected crystallised from ethyl acetate

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-ethoxyaniline (14.0 g.) and 4-benzyl-2-toluene-p-sulphonyloxymethylmorpholine (18.6 g.) is stirred and heated on the steam bath (95° C.) under nitrogen for 24 hours. The mixture is cooled and ether added. The solid thus obtained is collected and crystallised from ethyl acetate to give 4-benzyl-2-(2-ethoxyanilino)methylmorpholine toluene-p-sulphonate, m.p. 127° C. The toluene sulphonate salt is converted into the corresponding dihydrochloride by basifying it with dilute sodium hydroxide solution, extracting the base into ether (3× 200 ml.), washing the ethereal extract with water and then drying it over anhydrous magnesium sulphate followed by filtration and treatment of the ethereal solution of base with ethereal hydrochloric acid solution. The 4-benzyl-2-(2-ethoxyanilino)-methylmorpholine dihydrochloride melts at 226° C. after crystallisation from methanol/ethyl acetate. The mixture is cooled The solid thus obtained is collected crystallised from ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir: