N-methyl-N-phenyl-2-piperazin-1-ylacetamide

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

Procedure: The method followed that used to prepare 2-[4-(2-amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide (Example 6, Steps 1 to 6), but using 2-amino-4,5-dichloro-3-nitropyridine (0.036 g, 0.17 mmol), isopropanol (4.0 ml), and N-methyl-N-phenyl-2-piperazin-1-yl-acetamide (0.056 g, 0.24 mmol). Work-up and purification as described for 2-[4-(2-amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide afforded the title compound as an orange solid (0.039 g, 57%), 1H-NMR (500 Mz, DMSO-d6) 2.50 (obscured by DMSO peak, piperazine N(CH2)2), 2.96 (br s, 4H, piperazine N(CH2)2), 3.18 (s, 3H, NCH3), 6.94 (s, 2H, NH2), 7.35 (m, 3H) and 7.42 (m, 2H) (N-Ph), 8.05 (s, 1H, pyridine 6-H); LC-MS (ESI, m/z) 3.30 min—405, 407 [(M+H)+, Cl isotopic pattern]. purification

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

Procedure: 1.517 g of glutaric anhydride and then 1.715 g of N-[2-(piperazin-1-yl)acetyl]-N-methylaniline are added to 15 cm3 of dioxane. After stirring for 19 hours at 25° C., the white precipitate formed is filtered on No. 4 sintered glass, rinsed with dioxane and then with diethyl ether and then dried at 20° C. (90 Pa) to give 2 g of 5-[4-(methylphenylcarbamoylmethyl)piperazin-1-yl]-5-oxopentanoic acid in the form of a white solid which is used as it is. the white precipitate formed is filtered on No 4 sintered glass, rinsed with dioxane with diethyl ether and then dried at 20° C. (90 Pa)

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

Procedure: The method followed that used to prepare 2-[4-(2-amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide (Example 6, Steps 1 to 6), but using 2-amino-4,5-dichloro-3-nitropyridine (0.036 g, 0.17 mmol), isopropanol (4.0 ml), and N-methyl-N-phenyl-2-piperazin-1-yl-acetamide (0.056 g, 0.24 mmol). Work-up and purification as described for 2-[4-(2-amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide afforded the title compound as an orange solid (0.039 g, 57%), 1H-NMR (500 Mz, DMSO-d6) 2.50 (obscured by DMSO peak, piperazine N(CH2)2), 2.96 (br s, 4H, piperazine N(CH2)2), 3.18 (s, 3H, NCH3), 6.94 (s, 2H, NH2), 7.35 (m, 3H) and 7.42 (m, 2H) (N-Ph), 8.05 (s, 1H, pyridine 6-H); LC-MS (ESI, m/z) 3.30 min—405, 407 [(M+H)+, Cl isotopic pattern]. purification

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

Procedure: 1.517 g of glutaric anhydride and then 1.715 g of N-[2-(piperazin-1-yl)acetyl]-N-methylaniline are added to 15 cm3 of dioxane. After stirring for 19 hours at 25° C., the white precipitate formed is filtered on No. 4 sintered glass, rinsed with dioxane and then with diethyl ether and then dried at 20° C. (90 Pa) to give 2 g of 5-[4-(methylphenylcarbamoylmethyl)piperazin-1-yl]-5-oxopentanoic acid in the form of a white solid which is used as it is. the white precipitate formed is filtered on No 4 sintered glass, rinsed with dioxane with diethyl ether and then dried at 20° C. (90 Pa)

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

Procedure: 1.517 g of glutaric anhydride and then 1.715 g of N-[2-(piperazin-1-yl)acetyl]-N-methylaniline are added to 15 cm3 of dioxane. After stirring for 19 hours at 25° C., the white precipitate formed is filtered on No. 4 sintered glass, rinsed with dioxane and then with diethyl ether and then dried at 20° C. (90 Pa) to give 2 g of 5-[4-(methylphenylcarbamoylmethyl)piperazin-1-yl]-5-oxopentanoic acid in the form of a white solid which is used as it is. the white precipitate formed is filtered on No 4 sintered glass, rinsed with dioxane with diethyl ether and then dried at 20° C. (90 Pa)

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

Procedure: 1.517 g of glutaric anhydride and then 1.715 g of N-[2-(piperazin-1-yl)acetyl]-N-methylaniline are added to 15 cm3 of dioxane. After stirring for 19 hours at 25° C., the white precipitate formed is filtered on No. 4 sintered glass, rinsed with dioxane and then with diethyl ether and then dried at 20° C. (90 Pa) to give 2 g of 5-[4-(methylphenylcarbamoylmethyl)piperazin-1-yl]-5-oxopentanoic acid in the form of a white solid which is used as it is. the white precipitate formed is filtered on No 4 sintered glass, rinsed with dioxane with diethyl ether and then dried at 20° C. (90 Pa)

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

Procedure: The method followed that used to prepare 2-[4-(2-amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide (Example 6, Steps 1 to 6), but using 2-amino-4,5-dichloro-3-nitropyridine (0.036 g, 0.17 mmol), isopropanol (4.0 ml), and N-methyl-N-phenyl-2-piperazin-1-yl-acetamide (0.056 g, 0.24 mmol). Work-up and purification as described for 2-[4-(2-amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide afforded the title compound as an orange solid (0.039 g, 57%), 1H-NMR (500 Mz, DMSO-d6) 2.50 (obscured by DMSO peak, piperazine N(CH2)2), 2.96 (br s, 4H, piperazine N(CH2)2), 3.18 (s, 3H, NCH3), 6.94 (s, 2H, NH2), 7.35 (m, 3H) and 7.42 (m, 2H) (N-Ph), 8.05 (s, 1H, pyridine 6-H); LC-MS (ESI, m/z) 3.30 min—405, 407 [(M+H)+, Cl isotopic pattern]. purification

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

Procedure: 1.517 g of glutaric anhydride and then 1.715 g of N-[2-(piperazin-1-yl)acetyl]-N-methylaniline are added to 15 cm3 of dioxane. After stirring for 19 hours at 25° C., the white precipitate formed is filtered on No. 4 sintered glass, rinsed with dioxane and then with diethyl ether and then dried at 20° C. (90 Pa) to give 2 g of 5-[4-(methylphenylcarbamoylmethyl)piperazin-1-yl]-5-oxopentanoic acid in the form of a white solid which is used as it is. the white precipitate formed is filtered on No 4 sintered glass, rinsed with dioxane with diethyl ether and then dried at 20° C. (90 Pa)