dipropyl sulfate

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

Procedure: 4-Oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate was prepared according to method of esterification C from 194 mg (0.85 mmol) of 4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid, 1.29 mL (12.75 mmol) of triethylamine and 698 μL (1.1 mmol) of di-n-propylsulfate to give, after precipitation in water, 200 mg (87%) of 4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a beige solid. to give after precipitation in water

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

Procedure: This compound was prepared according to general method of esterification C from 294 mg (0.6 mmol) of 8-[3-(tert-butoxycarbonyl-methyl-amino)-pyrrolidine-1-sulfonyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid, 836 μL (6 mmol) of triethylamine and 492 μL (3 mmol) of di-n-propylsulfate to give, after purification by chromatography on silica (eluent dichloromethane/methanol 98/2), 155 mg (50%) of 8-[3-(tert-butoxycarbonyl-methyl-amino)-pyrrolidine-1-sulfonyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a brown solid. This compound was prepared to give after purification by chromatography on silica (eluent dichloromethane/methanol 98/2), 155 mg (50%) of 8-[3-(tert-butoxycarbonyl-methyl-amino)-pyrrolidine-1-sulfonyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a brown solid

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

Procedure: (S)-8-[(1-tert-butoxycarbony-pyrrolidin-2-ylmethyl)-cyclopropyl-sulfamoyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate is prepared according to synthesis 111, from 326 mg (1 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid and 288 mg (1.2 mmol) of (S)-1-tert-butoxycarbonyl-2-cyclopropylaminomethyl-pyrrolidine to give, after esterification according to general method C (using di-n-propylsulfate as the dialkylsulfate) and purification by chromatography on silica (eluent dichloromethane/methanol 99/1 then 95/5), 99 mg (17% in two stages) of (S)-8-[(1-tert-butoxycarbonyl-pyrrolidin-2-ylmethyl)-cyclopropyl-sulfamoyl]-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a white solid. to give purification by chromatography on silica (eluent dichloromethane/methanol 99/1

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

Procedure: 8-{[2-(tert-Butoxycarbonyl-isopropyl-amino)-ethyl]-cyclopropyl-sulfamoyl}-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate is prepared according to synthesis 111, from 326 mg (1 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid and 288 mg (1.2 mmol) of N-tert-butoxycarbonyl-N′-cyclopropyl-N-isopropyl-ethane-1,2-diamine to give, after esterification according to general method C (using di-n-propylsulfate as the dialkylsulfate) and purification by chromatography on silica (eluent cyclohexane/ethyl acetate 1/1 then 1/3), 201 mg (35% in two stages) of 8-{[2-(tert-butoxycarbonyl-isopropyl-amino)-ethyl]-cyclopropyl-sulfamoyl}-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a white solid. to give purification by chromatography on silica (eluent cyclohexane/ethyl acetate 1/1

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

Procedure: This compound is prepared according to synthesis 111, from 196 mg (0.6 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid, 242 μL (2.4 mmol) of triethylamine and 45 mg (0.66 mmol) of N-methyl-prop-2-ynyl-amine to give, after esterification according to general method C (using di-n-propylsulfate as the dialkylsulfate) and purification by chromatography on silica (eluent dichloromethane/methanol 97/3) then trituration in diethyl ether, 80 mg (33% in two stages) of 8-(methyl-prop-2-ynyl-sulfamoyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a white solid. This compound is prepared to give purification by chromatography on silica (eluent dichloromethane/methanol 97/3)

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

Procedure: 107 μL (0.76 mmol) of triethylamine and 100 μL (0.61 mmol) of di-n-propylsulfate are added to a solution of 150 mg (0.3 mmol) of 8-(1-tert-butoxycarbonyl-piperidin-4-ylsulfamoyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid dissolved in 2 mL of anhydrous dimethylformamide. The solution is stirred at room temperature for 20 hours then 43 μL (0.3 mmol) of triethylamine and 51 μL (0.3 mmol) of di-n-propylsulfate are added again. Stirring is continued for a further 24 hours and 3 mL of ammonia is added. After stirring for a further 15 minutes, water is added and the product is extracted with dichloromethane. The organic phases are dried over magnesium sulfate, filtered then evaporated. The residue is dissolved in 2 mL of dichloroethane and 1 mL of trifluoroacetic acid. The solution is stirred at room temperature for 1 hour then the solvents are evaporated. The solid is taken up in dichloromethane then triethylamine is added to release the amine. The solvents are evaporated again and the residue is purified by chromatography on silica (eluent chloroform/methanol/ammonia 160/25/4) to give 44 mg (33% in two stages) of 4-oxo-8-(piperidin-4-ylsulfamoyl)-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-propyl carboxylate in the form of a white solid. Stirring is continued for a further 24 hours After stirring for a further 15 minutes the product is extracted with dichloromethane The organic phases are dried over magnesium sulfate filtered then evaporated The residue is dissolved in 2 mL of dichloroethane The solution is stirred at room temperature for 1 hour the solvents are evaporated triethylamine is added The solvents are evaporated again the residue is purified by chromatography on silica (eluent chloroform/methanol/ammonia 160/25/4)

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

Procedure: 130 mg (0.35 mmol) of 3-acetyl-2-methyl-4-(2-methyl-4-oxo-4H-chromen-8-yl)-4,6-dihydro-1,6-naphthyridin-5(1H)-one are suspended in THF (8 ml), and 0.39 ml (0.39 mmol) of N′″-(tert-butyl)-N,N′,N″-tris[tris(dimethylamino)phosphoranylidene]phosphorimide triamide (phosphazene base P4-t-Bu; 1 M in hexane) is added. Then 68 μl (0.41 mmol) of di-n-propyl sulfate are added to the dark red solution. The decolorized solution is stirred for 10 min, then mixed with methanol and concentrated. The residue is purified by preparative HPLC to result in 63 mg (43% of theory) of the title compound as a white solid. concentrated The residue is purified by preparative HPLC

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 Grams of 3-acetyl-1-propanol was placed in a round-bottom flask, and 98 g of di-n-propylsulfuric acid and 90 ml of a 40% potassium hydroxide aqueous solution were concurrently dropwise added. The reaction temperature was maintained at 70 to 80° C. by adjusting the dropping amount. After the completion of the reaction, the reaction mixture was extracted with ether, and an ether layer was washed with water and then dried over anhydrous sodium sulfate. The ether was distilled off, and the remainder was vacuum-distilled for isolation and purification, to give 34.8 g of an end product (85° C./20 mmHg; yield 50%). After the completion of the reaction the reaction mixture was extracted with ether an ether layer was washed with water dried over anhydrous sodium sulfate The ether was distilled off the remainder was vacuum-distilled for isolation and purification

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 ml four necked flask equipped with a stirrer, a dropping funnel, a cooling tube and a thermometer, 4.96 g (0.05 mol) of 1-methyl piperidine and 5 ml of toluene were charged, after heating to 50° C., 10.02 g (0.055 mol) of dipropyl sulfuric acid was dropped slowly taking one hour or more. After reacting for 10 hours, 13.37 g of 1-methyl-3-propyl piperidinium propyl sulfate was obtained by drying under a reduced pressure. Then, 13.37 g of the obtained 1-methyl-3-propyl piperidinium propyl sulfate was dissolved in 8 ml of water, and a solution in which 10.5 g of potassium bis(fluorosulfonyl)imide was dissolved in 8 ml of water was added thereto at a room temperature and stirred. From separated two layers, the lower layer was fractionated and by-products were removed by adding 40 wt % of purified water and water washing five times, and vacuum drying was applied to obtain 15.31 g of 1-methyl-3-propyl pyrrolinium bis(fluorosulfonyl) imide. As a result of ICP analysis, the total alkali metals was 1.8 ppm, chloride ion was 0.5 ppm, and each of iodide and bromide ions was 0.1 ppm or less (lower than ICP detection limit). taking one hour or more