zinc;diacetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A starting compound (9)(14.0 mg, 22.8 μmol) was dissolved in 1 mL of chloroform. A saturated methanol solution of zinc acetate (0.3 mL) was added thereto and stirred at room temperature for 30 minutes. The chloroform solution was washed with water and solvent was removed by distillation. As a result, the compound (10) (14.6 mg) was obtained in a yield of 95%. The chloroform solution was washed with water and solvent was removed by distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A zinc salt of methotrexate was prepared as follows. Methotrexate (3.0 g, 0.0066 moles) was dissolved in 600 ml methanol at room temperature with rapid stirring. A solution of zinc acetate (0.6 g, 0.0033 moles) in 2 ml methanol was added dropwise to the methotrexate solution. Immediate precipitation (flocculent) was observed. The mixture was stirred for one hour at room temperature. The mixture was then concentrated in a rotating evaporator (roto-vap) at 40° C. The residue obtained (3.2 g) was dried under high vacuum. (C20H22N8O5)2Zn, MW 974.29; percent zinc: 6.46 (found), 6.71 (theoretical). Immediate precipitation (flocculent) The mixture was then concentrated in a rotating evaporator (roto-vap) at 40° C The residue obtained (3.2 g) was dried under high vacuum

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 30.3 g (0.3 mole) triethylamine, 18.3 g. (0.1 mole) zinc acetate, 55.0 g. (0.206 mole) 5-phenyl-2-trichloromethyloxazolidine and 15.6 g (0.206 mole) carbon disulfide was stirred at ambient temperatures for 17 hours and then was heated at 50°C, for three hours. A reddish amber-colored semi-solid was obtained after the volatile materials were distilled off at 50°/25 mm. Hg. The semi-solid was dissolved in methanol and the resulting solution added to water with vigorous stirring. the solids were filtered, air-dried, and redissolved in benzene. After drying the solution with magnesium sulfate, filtering the mixture and evaporating the solvent, 37 g. (58%) of the desired product (m.p. 91°-93°C.) was obtained; its infrared spectrum was consistent with the structure. A reddish amber-colored semi-solid was obtained after the volatile materials were distilled off at 50°/25 mm. Hg The semi-solid was dissolved in methanol the resulting solution added to water with vigorous stirring the solids were filtered air-dried redissolved in benzene After drying the solution with magnesium sulfate filtering the mixture evaporating the solvent, 37 g

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 30.3 g (0.3 mole) triethylamine, 18.3 g. (0.1 mole) zinc acetate, 55.0 g. (0.206 mole) 5-phenyl-2-trichloromethyloxazolidine and 15.6 g (0.206 mole) carbon disulfide was stirred at ambient temperatures for 17 hours and then was heated at 50°C, for three hours. A reddish amber-colored semi-solid was obtained after the volatile materials were distilled off at 50°/25 mm. Hg. The semi-solid was dissolved in methanol and the resulting solution added to water with vigorous stirring. the solids were filtered, air-dried, and redissolved in benzene. After drying the solution with magnesium sulfate, filtering the mixture and evaporating the solvent, 37 g. (58%) of the desired product (m.p. 91°-93°C.) was obtained; its infrared spectrum was consistent with the structure. A reddish amber-colored semi-solid was obtained after the volatile materials were distilled off at 50°/25 mm. Hg The semi-solid was dissolved in methanol the resulting solution added to water with vigorous stirring the solids were filtered air-dried redissolved in benzene After drying the solution with magnesium sulfate filtering the mixture evaporating the solvent, 37 g

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 500 ml isopropanol was added 30 g. (1.0 mole) of paraformaldehyde and 137 g. (1.0 mole) of 2-amino-1-phenylethanol, and the resulting mixture was stirred and heated at 50°C. After the solids had all dissolved, the solution was stirred an additional 30 minutes at 50°C. To the solution, cooled to 35°C., was added 68.7 g. (0.375 mole) of anhydrous zinc acetate and 76.0 g. (1.0 mole) of carbon disulfide. Solids formed in several minutes whereby additional isopropanol (400 ml) was added to stir the mixture efficiently. After heating at 55°C. for two hours, the mixture was cooled and filtered; the resulting solids were washed several times in a Waring Blendor with water, and air-dried overnight to obtain 184 g (95%) of the desired product melting at 220°-223°C.; its IR spectrum was consistent with the structure. To the solution, cooled to 35°C. was added 68.7 g was added to stir the mixture efficiently After heating at 55°C. for two hours the mixture was cooled filtered the resulting solids were washed several times in a Waring Blendor with water air-dried overnight

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 500 ml isopropanol was added 30 g. (1.0 mole) of paraformaldehyde and 137 g. (1.0 mole) of 2-amino-1-phenylethanol, and the resulting mixture was stirred and heated at 50°C. After the solids had all dissolved, the solution was stirred an additional 30 minutes at 50°C. To the solution, cooled to 35°C., was added 68.7 g. (0.375 mole) of anhydrous zinc acetate and 76.0 g. (1.0 mole) of carbon disulfide. Solids formed in several minutes whereby additional isopropanol (400 ml) was added to stir the mixture efficiently. After heating at 55°C. for two hours, the mixture was cooled and filtered; the resulting solids were washed several times in a Waring Blendor with water, and air-dried overnight to obtain 184 g (95%) of the desired product melting at 220°-223°C.; its IR spectrum was consistent with the structure. To the solution, cooled to 35°C. was added 68.7 g was added to stir the mixture efficiently After heating at 55°C. for two hours the mixture was cooled filtered the resulting solids were washed several times in a Waring Blendor with water air-dried overnight

反応条件: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thirty grams (1.0 mole) paraformaldehyde was added to a solution of 89.2 g. (1.0 mole) 2-amino-2-methyl-1-propanol in 600 ml. isopropanol, temperature at 45°-64°C. After all the paraformaldehyde had dissolved, the mixture was cooled to 12°C.; 92 g. (0.50 mole) anhydrous zinc acetate and 76 g. (1.0 mole) carbon disulfide were added. The reaction mixture was stirred six hours at 45°-50°C. Filtration at 5°C. gave 152.6 g. of the desired product melting with decomposition at 209°-211°C. A benzene-crystallized sample had the following analysis: at 45°-64°C Filtration at 5°C. gave 152.6 g

反応条件: temp:12.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thirty grams (1.0 mole) paraformaldehyde was added to a solution of 89.2 g. (1.0 mole) 2-amino-2-methyl-1-propanol in 600 ml. isopropanol, temperature at 45°-64°C. After all the paraformaldehyde had dissolved, the mixture was cooled to 12°C.; 92 g. (0.50 mole) anhydrous zinc acetate and 76 g. (1.0 mole) carbon disulfide were added. The reaction mixture was stirred six hours at 45°-50°C. Filtration at 5°C. gave 152.6 g. of the desired product melting with decomposition at 209°-211°C. A benzene-crystallized sample had the following analysis: at 45°-64°C Filtration at 5°C. gave 152.6 g

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While cooling and stirring at 10°C, 76.8 g. (0.50 mole) 2,2-dimethylthiazolidine hydrochloride [preparation described by B. Sweetman et al, J. Med. Chem. 12, 888 (1969)] was added to a mixture of 30 ml isopropanol and 101 g. (1.00 mole) triethylamine. Likewise, 38.0 g. (0.50 mole) of carbon disulfide was gradually added, followed by 45.8 g. (0.25 mole) of anhydrous zinc acetate. After standing overnight at room temperature, the precipitate was filtered, twice water-washed with 1 liter portions of water and air-dried to give 80.5 g. of the yellow product melting at 148° - 153°C (decomp.) and having the following analysis: Found: C, 31.51; H, 4.70%. Calcd for C12H20N2S6Zn: C, 32.04; H, 4.45%. While cooling the precipitate was filtered twice water-washed with 1 liter portions of water air-dried to give 80.5 g

反応条件: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While cooling and stirring at 10°C, 76.8 g. (0.50 mole) 2,2-dimethylthiazolidine hydrochloride [preparation described by B. Sweetman et al, J. Med. Chem. 12, 888 (1969)] was added to a mixture of 30 ml isopropanol and 101 g. (1.00 mole) triethylamine. Likewise, 38.0 g. (0.50 mole) of carbon disulfide was gradually added, followed by 45.8 g. (0.25 mole) of anhydrous zinc acetate. After standing overnight at room temperature, the precipitate was filtered, twice water-washed with 1 liter portions of water and air-dried to give 80.5 g. of the yellow product melting at 148° - 153°C (decomp.) and having the following analysis: Found: C, 31.51; H, 4.70%. Calcd for C12H20N2S6Zn: C, 32.04; H, 4.45%. While cooling the precipitate was filtered twice water-washed with 1 liter portions of water air-dried to give 80.5 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While cooling and stirring 250 g. of pyridine, 175 g. (1.40 moles) of thiazolidine hydrochloride [preparation described by S. Ratner and H. Clarke, J. Am. Chem. Soc. 59, 200 (1937)] was added. After it had dissolved, 106.4 g. (1.40 mole) of carbon disulfide was added dropwise, followed by 128.5 g. (0.70 mole) of anhydrous zinc acetate. The resulting reaction mixture was stirred at 40° - 50°C for 2 hours. The precipitate was filtered at 5° - 10°C. The crude solid was water-washed and finally freed of pyridine by vacuum-drying at 120°C to give 147.8 g. of the desired product. It gradually decomposed starting at ca. 200°C without a definite final decomposition point. A small sample washed with hot benzene had the following analysis: Found: C, 24.46; H, 2.95; N, 7.31; Zn, 16.58%. Calcd for C8H12N2S6Zn: C, 24.40; H, 3.05; N, 7.12; Zn, 16.62%. While cooling After it had dissolved The resulting reaction mixture was stirred at 40° - 50°C for 2 hours The precipitate was filtered at 5° - 10°C washed by vacuum-drying at 120°C to give 147.8 g

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: While cooling and stirring 250 g. of pyridine, 175 g. (1.40 moles) of thiazolidine hydrochloride [preparation described by S. Ratner and H. Clarke, J. Am. Chem. Soc. 59, 200 (1937)] was added. After it had dissolved, 106.4 g. (1.40 mole) of carbon disulfide was added dropwise, followed by 128.5 g. (0.70 mole) of anhydrous zinc acetate. The resulting reaction mixture was stirred at 40° - 50°C for 2 hours. The precipitate was filtered at 5° - 10°C. The crude solid was water-washed and finally freed of pyridine by vacuum-drying at 120°C to give 147.8 g. of the desired product. It gradually decomposed starting at ca. 200°C without a definite final decomposition point. A small sample washed with hot benzene had the following analysis: Found: C, 24.46; H, 2.95; N, 7.31; Zn, 16.58%. Calcd for C8H12N2S6Zn: C, 24.40; H, 3.05; N, 7.12; Zn, 16.62%. While cooling After it had dissolved The resulting reaction mixture was stirred at 40° - 50°C for 2 hours The precipitate was filtered at 5° - 10°C washed by vacuum-drying at 120°C to give 147.8 g