methyl 4-oxothiolane-3-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-oxotetrahydro thiophene-3-carboxylic acid methyl ester (4 g, 25 mmol) in methanol (7 ml), cooled at 0° C., a solution of potassium cyanide (1.68 g, 30 mmol) in water (10 ml) was added. The mixture was acidified with acetic acid (1.5 ml, 25 mmol) and stirred at 0° C. for 8 hours. Then the mixture was acidified with H3PO4 and diluted with brine (50 ml) and extracted with CH2Cl2 (4×30 ml). The organic layers were dried over sodium sulfate and concentrated to give 4-cyano-tetrahydro thiophene-3-carboxylic acid methyl ester in 75% yield. extracted with CH2Cl2 (4×30 ml) The organic layers were dried over sodium sulfate concentrated

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

実験手順: A solution of methyl-4-oxo-tetrahydro-thiophene-3-carboxylate (5.75 g, 35.9 mmol) and 2-fluoro-4-iodo-aniline (9.4 g, 40.9 mmol) were heated to reflux in a mixture of ethanol (25 mL) and acetic acid (0.3 mL) for 18 hours. The solution was cooled to room temperature, filtered and the solid product dried in vacuo to provide methyl-4-(2-fluoro-4-iodo-phenylamino)-2,3-dihydro-thiophene-3-carboxylate (5.70 g, 42% yield). MS (EI) for C12H11FINO2S: 380 (MH+). filtered the solid product dried in vacuo

反応条件: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 320 g. portion of methyl tetrahydro-4-oxo-3-thiophenecarboxylate [Hromatka et al., Monat. Chemie, 104, 1520 (1973)] is dissolved in 650 ml. of isopropenylacetate, 2.0 g. of p-toluenesulfonic acid is added and the mixture is refluxed overnight. The mixture is concentrated, dissolved in 750 ml. of methylene chloride, cooled to -25° C. and 160 ml. of sulfuryl chloride is added over a one hour period. The methylene chloride is distilled off giving 4-acetoxy-3-thiophenecarboxylic acid methyl ester. the mixture is refluxed overnight The mixture is concentrated dissolved in 750 ml of sulfuryl chloride is added over a one hour period The methylene chloride is distilled off

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

実験手順: 3-Oxo-4-methoxycarbonyltetrahydrothiophene (28 g) was heated under reflux for 1 hour with hydroxylamine hydrochloride (11.5 g) in methanol (80 ml). The mixture was then cooled and a first crop was filtered off and washed with dry diethyl ether to afford the title compound (18.4 g, 57.6%) m.p. 203° to 205° C. On further cooling a second crop (2.7 g, 8.5%) was obtained, m.p. 201° to 202° C. The total yield was thus 66.1%. The mixture was then cooled a first crop was filtered off washed with dry diethyl ether

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

実験手順: 4-Oxo-3-methoxycarbonyltetrahydrothiophene (3.9 g) was heated under reflux for 1 hour with hydroxylamine hydrochloride (2 g) in acetonitrile 10 ml). The mixture was then cooled and the solid portion was filtered off and washed with dry diethyl ether to afford the title compound (3.65 g), m.p. 203°-204° C. The mixture was then cooled the solid portion was filtered off washed with dry diethyl ether

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

実験手順: To 19.1 g (0.15 mole) of 5-amino-3-dimethylamino-1H-1,2,4-triazole dissolved in 15 ml of acetic acid 24.3 g (0.15 moles) of methyl 4-oxo-tetrahydrothiophene-3-carboxylate are added and the reaction mixture is boiled for 15 minutes. The product precipitated from the reaction mixture is filtered off from the hot solution, then washed with i-propanol and recrystallized from dimethylformamide. Thus 26.1 g (73.3%) of 2-dimethylamino-6,8-dihydrothieno[3,4-d]-1,2,4-triazolo-[1,5-a]pyrimidine-5(9H)-one are obtained. Melting point: 355°-360° C. are added The product precipitated from the reaction mixture is filtered off from the hot solution washed with i-propanol recrystallized from dimethylformamide

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

実験手順: To 19.1 g (0.15 mole) of 5-amino-3-dimethylamino-1H-1,2,4-triazole dissolved in 15 ml of acetic acid 24.3 g (0.15 moles) of methyl 4-oxo-tetrahydrothiophene-3-carboxylate are added and the reaction mixture is boiled for 15 minutes. The product precipitated from the reaction mixture is filtered off from the hot solution, then washed with i-propanol and recrystallized from dimethylformamide. Thus 26.1 g (73.3%) of 2-dimethylamino-6,8-dihydrothieno[3,4-d]-1,2,4-triazolo-[1,5-a]pyrimidine-5(9H)-one are obtained. Melting point: 355°-360° C. are added The product precipitated from the reaction mixture is filtered off from the hot solution washed with i-propanol recrystallized from dimethylformamide

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

実験手順: Ethyl 6-aminonicotinate (2.5 g., 0.015 mol), methyl 4-oxotetrahydrothiophene-3-carboxylate (6.2 g., 0.039 mol) and p-toluenesulfonic acid monohydrate (0.25 g) are thoroughly mixed and heated at 155°-160° C. under nitrogen for 90 minutes. The distillate is collected in a Dean-Stark trap. The residue is cooled, triturated with boiling ethanol and filtered. Recrystallization from methanol gives yellow crystals (1.2 g.), mp 183°-185° C. heated at 155°-160° C. under nitrogen for 90 minutes The distillate is collected in a Dean-Stark trap The residue is cooled triturated with boiling ethanol filtered Recrystallization from methanol gives yellow crystals (1.2 g.), mp 183°-185° C.

反応条件: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Aminonicotinic acid (10 g., 0.072 mol) [Berichte, 26, 2187, (1893)], methyl 4-oxotetrahydro-thiophene-3-carboxylate (28 g., 0.175 mol) [Monats, Chem., 104, 1520(1973)] and p-toluenesulfonic acid monohydrate (1.0 g) are thoroughly mixed and heated at 170° C. under nitrogen for 75 minutes. The distillate is collected in a Dean-Stark trap. The residue is cooled, tritrated with boiling chloroform and filtered to give the product as a yellow powder (11.3 g.). Recrystallization from dimethylformamide gives an analytical sample mp 314°-315° C. (dec). The distillate is collected in a Dean-Stark trap The residue is cooled filtered

反応条件: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-Aminonicotinic acid (10 g., 0.072 mol) [Berichte, 26, 2187, (1893)], methyl 4-oxotetrahydro-thiophene-3-carboxylate (28 g., 0.175 mol) [Monats, Chem., 104, 1520(1973)] and p-toluenesulfonic acid monohydrate (1.0 g) are thoroughly mixed and heated at 170° C. under nitrogen for 75 minutes. The distillate is collected in a Dean-Stark trap. The residue is cooled, tritrated with boiling chloroform and filtered to give the product as a yellow powder (11.3 g.). Recrystallization from dimethylformamide gives an analytical sample mp 314°-315° C. (dec). The distillate is collected in a Dean-Stark trap The residue is cooled filtered