methyl 3-(cyclohexylamino)propanoate

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

Procedure: Cyclohexylamine (Aldrich; 17 g, 0.174 mol) was dissolved in THF (300 mL). To this was added methyl acrylate (Aldrich; 15 g, 0.174 mol) in one portion. The reaction mixture was stirred over the weekend. The solvent was evaporated with care due to the volatility of the product and the residue distilled at 72° C. at 0.30 mbar to yield the title compound as a clear oil (23.7 g, 74%). The solvent was evaporated with care due to the volatility of the product the residue distilled at 72° C. at 0.30 mbar

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

Procedure: Cyclohexylamine (Aldrich; 17 g, 0.174 mol) was dissolved in THF (300 mL). To this was added methyl acrylate (Aldrich; 15 g, 0.174 mol) in one portion. The reaction mixture was stirred over the weekend. The solvent was evaporated with care due to the volatility of the product and the residue distilled at 72° C. at 0.30 mbar to yield the title compound as a clear oil (23.7 g, 74%). The solvent was evaporated with care due to the volatility of the product the residue distilled at 72° C. at 0.30 mbar

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4-dichloro-5-nitropyrimidine (Aldrich; 10 g, 0.052 mol) was dissolved in THF (250 mL). To this was added DIPEA (11 mL, 0.062 mol) and the reaction cooled to 0° C. Methyl3-(cyclohexylamino)propanoate (9.5 g, 0.052 mol) in THF (30 mL) was slowly added. The cooling bath was removed and the reaction was stirred at room temperature for 1 hour. To the reaction mixture was added saturated NH4OH(aq) (100 mL), and the reaction heated at 55° C. for 4 hours using a dry ice condenser. The reaction mixture was extracted with DCM (3×100 ml), and combined organic extracts dried and evaporated. The residue was dissolved in methanol (200 mL). Ammonium formate (33 g, 0.52 mol) and 10% palladium (1.5 g) were added. The reaction was heated at reflux for 5 hours, filtered and the methanol evaporated to yield a dark orange solid, which was quenched with 2.0 N NaOH(aq) (100 mL), extracted with DCM (3×150 mL), and combined extracts dried and evaporated to yield an orange solid. Hot acetonitrile was added, this was stirred and then sonicated to give a precipitate that was filtered and dried to yield the title compound as a yellow solid (7.5 g, 55%). The cooling bath was removed To the reaction mixture was added saturated NH4OH(aq) (100 mL) the reaction heated at 55° C. for 4 hours The reaction mixture was extracted with DCM (3×100 ml) dried evaporated The residue was dissolved in methanol (200 mL) The reaction was heated at reflux for 5 hours filtered the methanol evaporated to yield a dark orange solid, which was quenched with 2.0 N NaOH(aq) (100 mL) extracted with DCM (3×150 mL) dried evaporated to yield an orange solid this was stirred sonicated to give a precipitate that was filtered dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4-dichloro-5-nitropyrimidine (Aldrich; 10 g, 0.052 mol) was dissolved in THF (250 mL). To this was added DIPEA (11 mL, 0.062 mol) and the reaction cooled to 0° C. Methyl3-(cyclohexylamino)propanoate (9.5 g, 0.052 mol) in THF (30 mL) was slowly added. The cooling bath was removed and the reaction was stirred at room temperature for 1 hour. To the reaction mixture was added saturated NH4OH(aq) (100 mL), and the reaction heated at 55° C. for 4 hours using a dry ice condenser. The reaction mixture was extracted with DCM (3×100 ml), and combined organic extracts dried and evaporated. The residue was dissolved in methanol (200 mL). Ammonium formate (33 g, 0.52 mol) and 10% palladium (1.5 g) were added. The reaction was heated at reflux for 5 hours, filtered and the methanol evaporated to yield a dark orange solid, which was quenched with 2.0 N NaOH(aq) (100 mL), extracted with DCM (3×150 mL), and combined extracts dried and evaporated to yield an orange solid. Hot acetonitrile was added, this was stirred and then sonicated to give a precipitate that was filtered and dried to yield the title compound as a yellow solid (7.5 g, 55%). The cooling bath was removed To the reaction mixture was added saturated NH4OH(aq) (100 mL) the reaction heated at 55° C. for 4 hours The reaction mixture was extracted with DCM (3×100 ml) dried evaporated The residue was dissolved in methanol (200 mL) The reaction was heated at reflux for 5 hours filtered the methanol evaporated to yield a dark orange solid, which was quenched with 2.0 N NaOH(aq) (100 mL) extracted with DCM (3×150 mL) dried evaporated to yield an orange solid this was stirred sonicated to give a precipitate that was filtered dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,4-dichloro-5-nitropyrimidine (Aldrich; 10 g, 0.052 mol) was dissolved in THF (250 mL). To this was added DIPEA (11 mL, 0.062 mol) and the reaction cooled to 0° C. Methyl3-(cyclohexylamino)propanoate (9.5 g, 0.052 mol) in THF (30 mL) was slowly added. The cooling bath was removed and the reaction was stirred at room temperature for 1 hour. To the reaction mixture was added saturated NH4OH(aq) (100 mL), and the reaction heated at 55° C. for 4 hours using a dry ice condenser. The reaction mixture was extracted with DCM (3×100 ml), and combined organic extracts dried and evaporated. The residue was dissolved in methanol (200 mL). Ammonium formate (33 g, 0.52 mol) and 10% palladium (1.5 g) were added. The reaction was heated at reflux for 5 hours, filtered and the methanol evaporated to yield a dark orange solid, which was quenched with 2.0 N NaOH(aq) (100 mL), extracted with DCM (3×150 mL), and combined extracts dried and evaporated to yield an orange solid. Hot acetonitrile was added, this was stirred and then sonicated to give a precipitate that was filtered and dried to yield the title compound as a yellow solid (7.5 g, 55%). The cooling bath was removed To the reaction mixture was added saturated NH4OH(aq) (100 mL) the reaction heated at 55° C. for 4 hours The reaction mixture was extracted with DCM (3×100 ml) dried evaporated The residue was dissolved in methanol (200 mL) The reaction was heated at reflux for 5 hours filtered the methanol evaporated to yield a dark orange solid, which was quenched with 2.0 N NaOH(aq) (100 mL) extracted with DCM (3×150 mL) dried evaporated to yield an orange solid this was stirred sonicated to give a precipitate that was filtered dried