pentanimidamide;hydrochloride

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

Procedure: A solution of 3.0 g valeramidine hydrochloride, 3.47 g ethyl 2-ethylacetoacetate, and 5.8 mL triethylamine in 20 mL DMF was heated to 120° C. for 18 hours. The mixture was diluted with brine and extracted three times with ether. The combined organic material was washed with brine, was dried over MgSO4, was stripped of solvent in vacuo, and then was still flash chromatographed in 3% MeOH in CH2Cl2 to give the title compound as a white solid. extracted three times with ether The combined organic material was washed with brine was dried over MgSO4 chromatographed in 3% MeOH in CH2Cl2

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

Procedure: Sodium hydride (2.82 g, 0.117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

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

Procedure: To a mixture of 2.2 g of 4-oxo-1,3-piperidinedicarboxylic acid 3-ethyl 1-[2-(trimethylsilyl)ethyl]ester and 1.2 g of valeramidine hydrochloride in 15 ml of dry ethyl alcohol is added 7 ml of 1M sodium methoxide in methanol. The resulting mixture is stirred and heated under reflux for 25 minutes. The reaction mixture is allowed to cool, filtered and the solid washed with ethyl alcohol. The combined filtrates are evaporated in vacuo without heat to give an oily solid. Ether and water are added to the residue followed by refrigeration. The resulting crystalline solid is collected, washed with ether and air dried to give 0.8 g of the desired product as a crystalline solid, m.p. 152°-155° C. heated under reflux for 25 minutes to cool filtered the solid washed with ethyl alcohol The combined filtrates are evaporated in vacuo without heat to give an oily solid The resulting crystalline solid is collected washed with ether and air dried

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

Procedure: To a mixture of 2.2 g of 4-oxo-1,3-piperidinedicarboxylic acid 3-ethyl 1-[2-(trimethylsilyl)ethyl]ester and 1.2 g of valeramidine hydrochloride in 15 ml of dry ethyl alcohol is added 7 ml of 1M sodium methoxide in methanol. The resulting mixture is stirred and heated under reflux for 25 minutes. The reaction mixture is allowed to cool, filtered and the solid washed with ethyl alcohol. The combined filtrates are evaporated in vacuo without heat to give an oily solid. Ether and water are added to the residue followed by refrigeration. The resulting crystalline solid is collected, washed with ether and air dried to give 0.8 g of the desired product as a crystalline solid, m.p. 152°-155° C. heated under reflux for 25 minutes to cool filtered the solid washed with ethyl alcohol The combined filtrates are evaporated in vacuo without heat to give an oily solid The resulting crystalline solid is collected washed with ether and air dried

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

Procedure: A solution of 3.0 g valeramidine hydrochloride, 3.47 g ethyl 2-ethylacetoacetate, and 5.8 mL triethylamine in 20 mL DMF was heated to 120° C. for 18 hours. The mixture was diluted with brine and extracted three times with ether. The combined organic material was washed with brine, was dried over MgSO4, was stripped of solvent in vacuo, and then was still flash chromatographed in 3% MeOH in CH2Cl2 to give the title compound as a white solid. extracted three times with ether The combined organic material was washed with brine was dried over MgSO4 chromatographed in 3% MeOH in CH2Cl2

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

Procedure: A solution of 3.0 g valeramidine hydrochloride, 3.47 g ethyl 2-ethylacetoacetate, and 5.8 mL triethylamine in 20 mL DMF was heated to 120° C. for 18 hours. The mixture was diluted with brine and extracted three times with ether. The combined organic material was washed with brine, was dried over MgSO4, was stripped of solvent in vacuo, and then was still flash chromatographed in 3% MeOH in CH2Cl2 to give the title compound as a white solid. extracted three times with ether The combined organic material was washed with brine was dried over MgSO4 chromatographed in 3% MeOH in CH2Cl2

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

Procedure: Sodium hydride (2.82 g, 0,117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

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

Procedure: Sodium hydride (2.82 g, 0,117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution

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

Procedure: A solution of 3.0 g valeramidine hydrochloride, 3.47 g ethyl-2 ethylacetoacetate, and 5.8 mL triethylamine in 20 mL DMF was heated to 120° C. for 18 hours. The mixture was diluted with brine and extracted three times with ether. The combined organic material was washed with brine, was dried over MgSO4, was stripped of solvent in vacuo, and then was still flash chromatographed in 3% MeOH in CH2Cl2 to give the title compound as a white solid. extracted three times with ether The combined organic material was washed with brine was dried over MgSO4 chromatographed in 3% MeOH in CH2Cl2

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

Procedure: A solution of 3.0 g valeramidine hydrochloride, 3.47 g ethyl 2-ethylacetoacetate, and 5.8 mL triethylamine in 20 mL DMF was heated to 120° C. for 18 hours. The mixture was diluted with brine and extracted three times with ether. The combined organic material was washed with brine, was dried over MgSO4, was stripped of solvent in vacuo, and then was still flash chromatographed in 3% MeOH in CH2Cl2 to give the title compound as a white solid. extracted three times with ether The combined organic material was washed with brine was dried over MgSO4 chromatographed in 3% MeOH in CH2Cl2

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

Procedure: A solution of 4.5 g valeramidine hydrochloride, 1.9 mg sodium methoxide, and 1.0 g ethyl 2-(2-chlorophenyl)acetoacetate in 20 mL DMF was heated to 150° C. for 20 hours. After cooling to room temperature, the reaction mixture was poured into a mixture of brine and saturated ammonium chloride solutions then was extracted three times with ether. The combined organic material was dried over MgSO4, stripped of solvent in vacuo, and MPLC'd in 40% ethyl acetate/hexane to give 212 mg of the title compound as a white solid, 37% yield. Rf 0.17 in 40% ethyl acetate/hexane; 1H NMR (300 MHz, CDCl3) δ7.55 (m, 1H), 7.38 (m, 2H), 7.26 (m, 1H), 4.64 (br s, 1H), 2.74 (3 line m, 2H), 2.11 (s, 3H), 1.79 (m, 2H), 1.42 (6 line m, 2H), 0.96 (t, 3H). then was extracted three times with ether The combined organic material was dried over MgSO4

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

Procedure: Sodium hydride (2.82 g, 0,117 mol) was dissolved in 30 ml of absolute ethanol at 0° C. Valeramidine hydrochloride (16.71 g, 0.123 mol) was added to this solution, and after 15 minutes the solution was filtered and the collected solid was washed with 20 ml of ethanol and 50 ml of benzene. The combined filtrates were diluted with 750 ml of benzene, 15 g (0.117 mol) of methyl 3-formylacrylate was added, and the mixture was refluxed for 18.5 h using a trap to remove water. The solvents were removed under vacuum and the residue slurried in ether. Evaporation of the ether solution gave the title compound as an oil. after 15 minutes the solution was filtered the collected solid was washed with 20 ml of ethanol and 50 ml of benzene was added the mixture was refluxed for 18.5 h to remove water The solvents were removed under vacuum Evaporation of the ether solution