31.0 %Chromat. |
With potassium carbonate In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
3.2 %Chromat. |
With potassium carbonate In methanol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
1.1 %Chromat. |
With triethylamine In isopropyl alcohol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
5.5 %Chromat. |
With triethylamine In 1,2-dimethoxyethane at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
20.7 %Chromat. |
With triethylamine In acetonitrile at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
5.4 %Chromat. |
With triethylamine In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
5.0 %Chromat. |
With triethylamine In methanol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
2.7 %Chromat. |
With N-ethyl-N,N-diisopropylamine In isopropyl alcohol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
1.6 %Chromat. |
With N-ethyl-N,N-diisopropylamine In 1,2-dimethoxyethane at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
16.1 %Chromat. |
With N-ethyl-N,N-diisopropylamine In acetonitrile at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
2.8 %Chromat. |
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
1.8 %Chromat. |
With N-ethyl-N,N-diisopropylamine In methanol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
0.9 %Chromat. |
With caesium carbonate In isopropyl alcohol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
3.6 %Chromat. |
With caesium carbonate In 1,2-dimethoxyethane at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
0.2 %Chromat. |
With caesium carbonate In acetonitrile at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
3.6 %Chromat. |
With caesium carbonate In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
9.3 %Chromat. |
With potassium hydroxide In isopropyl alcohol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
14.5 %Chromat. |
With potassium hydroxide In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
2.2 %Chromat. |
With pyridine In isopropyl alcohol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
4.2 %Chromat. |
With pyridine In 1,2-dimethoxyethane at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
11.0 %Chromat. |
With pyridine In acetonitrile at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
6.9 %Chromat. |
With pyridine In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
5.9 %Chromat. |
With pyridine In methanol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
10.0 %Chromat. |
With sodium hydroxide In isopropyl alcohol at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
5.0 %Chromat. |
With sodium hydroxide In tetrahydrofuran at 80 - 85℃; for 6 h; |
A series of experiments was run to determine the effect of solvent and base on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]- N'-cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2,6- difluorobenzoyl hydrazide (0. 3g, 1.74 mmol) in 15mol of the selected solvent (See Table 4 below) was stirred during the addition of (2.08 mmol, 1.3 equivalents) of the selected base (See Table 4 below). The reaction mixture was heated to about 80-85°C and maintained at this temperature for 6h. After cooling the reaction mixture to about 20-25°C an aliqout was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 4 below. Table 4: Effect of Solvent and Base on Title Product Yield a, b Solvent MeOH THF DME IPA MeCN base = K2CO3 percent yield 3. 2 31. 0 17. 5 13. 6 3. 0 base = Cs2CO3 percent yield 0.0 3.6 3.6 0.9 0.2 base = TEA percent yield 5.0 5.4 5.5 1.1 20.7c base = DIPEA percent yield 1.8 2.8 1.6 2.7 16.1d base = Pyridine percent yield 5.9 6.9 4.2 2.2 11.0 base = KOHe percent yield 14. 5 9. 3 base = NaOH pellets percent yield 5.0 10.0 HPLC Apercent conversion to the title compound b Varying amounts of isourea exchange products and decomposition were observed in all cases except for those using pyridine c HPLC analysis showed-3percent of another regioisomer d HPLC analysis showed ~1. 4percent of another regioisomer e pellets |
0.3 %Chromat. |
at 80 - 85℃; |
A series of experiments was run to determine the effect of solvent on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]-N'- cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2, 6-difluorobenzoyl hydrazide (0.3 g, 1.74 mmol) in 15ml of the selected solvent (see Table 3 below) was stirred and heated to about 80-85°C. The reaction mixture was maintained at about 80-85°C overnight. After cooling the reaction mixture to about 20-25°C an aliquot was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 3 below. Table 3: Effect of Solvent on Title Product Yield a Solvent MeOH THF DME IPA MeCN percent Yield 2.3 3.0 1.0 0.3 1.8 a HPLC Apercent conversion to title compound |
1.0 %Chromat. |
at 80 - 85℃; |
A series of experiments was run to determine the effect of solvent on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]-N'- cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2, 6-difluorobenzoyl hydrazide (0.3 g, 1.74 mmol) in 15ml of the selected solvent (see Table 3 below) was stirred and heated to about 80-85°C. The reaction mixture was maintained at about 80-85°C overnight. After cooling the reaction mixture to about 20-25°C an aliquot was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 3 below. Table 3: Effect of Solvent on Title Product Yield a Solvent MeOH THF DME IPA MeCN percent Yield 2.3 3.0 1.0 0.3 1.8 a HPLC Apercent conversion to title compound |
1.8 %Chromat. |
at 80 - 85℃; |
A series of experiments was run to determine the effect of solvent on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]-N'- cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2, 6-difluorobenzoyl hydrazide (0.3 g, 1.74 mmol) in 15ml of the selected solvent (see Table 3 below) was stirred and heated to about 80-85°C. The reaction mixture was maintained at about 80-85°C overnight. After cooling the reaction mixture to about 20-25°C an aliquot was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 3 below. Table 3: Effect of Solvent on Title Product Yield a Solvent MeOH THF DME IPA MeCN percent Yield 2.3 3.0 1.0 0.3 1.8 a HPLC Apercent conversion to title compound |
3.0 %Chromat. |
at 80 - 85℃; |
A series of experiments was run to determine the effect of solvent on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]-N'- cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2, 6-difluorobenzoyl hydrazide (0.3 g, 1.74 mmol) in 15ml of the selected solvent (see Table 3 below) was stirred and heated to about 80-85°C. The reaction mixture was maintained at about 80-85°C overnight. After cooling the reaction mixture to about 20-25°C an aliquot was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 3 below. Table 3: Effect of Solvent on Title Product Yield a Solvent MeOH THF DME IPA MeCN percent Yield 2.3 3.0 1.0 0.3 1.8 a HPLC Apercent conversion to title compound |
2.3 %Chromat. |
at 80 - 85℃; |
A series of experiments was run to determine the effect of solvent on the HPLC determined yield of the title product. The general procedure for the experiments was as follows. A mixture of N- [4- (aminosulfonyl) phenyl]-N'- cyanocarbamidic acid phenyl ester (0.5 g, 1.60 mmol) and 2, 6-difluorobenzoyl hydrazide (0.3 g, 1.74 mmol) in 15ml of the selected solvent (see Table 3 below) was stirred and heated to about 80-85°C. The reaction mixture was maintained at about 80-85°C overnight. After cooling the reaction mixture to about 20-25°C an aliquot was removed for HPLC analysis. An HPLC sample was prepared by diluting the aliquot with acetonitrile and water (50/50) to determine percent conversion to the title compound, with results as listed in Table 3 below. Table 3: Effect of Solvent on Title Product Yield a Solvent MeOH THF DME IPA MeCN percent Yield 2.3 3.0 1.0 0.3 1.8 a HPLC Apercent conversion to title compound |