5-(5-Chlorosulfonyl-2-ethoxyphenyl)-1-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one

Off-White Solid

Chlorosulfuric acid (50 ml) was added into a 100 ml three-neck flask with a stirrer, 5-(2-ethoxy)-phenyl-1-methyl-3-n-propyl-1, 6-dihydro-7H-pyrazolo[4, 3-d]pyrimidine-7-one (31.2 g (0.1 mol)) was added in batches under stirring in an ice bath. The reaction was exothermic and was performed for 12 hrs. The reaction solution was slowly poured into icy water (100 g), a white solid was separated out, filtered, dried. A white solid (30 g) was obtained with a yield of 76percent.4. Preparation of 5-(2-ethoxyphenyl-5-chlorosulphonyl)-1-methyl-3-propyl-1, 6-dihydro-7H-pyrazolo[4, 3-d]pyrimidine-7-ketone (ZTH-4): [0031] At a temperature of −10° C., adding 5-(2-ethoxyphenyl)-1-methyl-3-propyl-1, 6-dihydro-7H-pyrazolo[4, 3-d]pyrimidine-7-ketone (50 g, 160 mmo) into 100 ml chlorosulfonic acid, keeping the reaction solution at temperature no greater than 25° C. during dropping; upon dropping completes, reacting under room temperature for 3 hours; pouring the reaction liquid into crushed ice, mechanically stirring, keeping the temperature no greater than 25° C.; and then stirring under room temperature for 1 hour, filtering and drying, 50 g white solid ZTH-4 is obtained, wherein the yield is 75.9percent.Step 8: Synthesis of 4-ethoxy-3-(6, 7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4, 3-d] pyrimidin-5-yl) benzene-1-sulfonyl chloride:- To the chlorosulphonic acid (10 eq) was added 5-(2-ethoxyphenyl)- 1 -methyl-3-propyl- 1 H-pyrazolo[4, 3 -d]pyrimidin-7(6H)- one (1 eq) while maintaining the temperature 0 °C. Then reaction was allowed toproceed at 5 °C until TLC analysis indicated the absence of starting material. After the reaction was completed then cooled CHC13 and ice in ice bath was added to the reaction mixture. Organic layer was separated. Water layer was re-extracted with 2 x 100 ml cold CHC13 and the combined organic layer are washed with brine solution, concentrated under vacuum; Yield 75percent. ‘H NMR (400 MHz, CDC13) 6 10.78(s 1H), 8.72 (d, J= 1.4Hz, 1H), 8.04 (dd, J = 7.5, 1.4 Hz, 1H), 7.33 (d, J 7.5 Hz, 1H), 4.38(q J =6.8Hz2H), 4.27(s 3H), 2.92(t J= 7.6 Hz 2H), l.87(m 2H), 1.65(t J= 6.8Hz 3H). l.02(t J=7.2Hz 3H). ESI [M + H] : 411.13At a temperature of -10°C, adding 5-(2- ethoxyphenyl)-1- methyl-3- propyl-1, 6-dihydro-7H-pyrazolo[4, 3-d]pyrimidine-7-ketone (50g, 160mmo) into 100ml chlorosulfonic acid, keeping the reaction solution at temperature no greaterthan 25°C during dropping; upon dropping completes, reacting under room temperature for 3 hours; pouring the reactionliquid into crushed ice, mechanically stirring, keeping the temperature no greater than 25°C; and then stirring under roomtemperature for 1 hour, filtering and drying, 50g white solid ZTH-4 is obtained, wherein the yield is 75.9percent.I-09a (2.5 g, 8.0 mmol) was added into CISO3H (R-05, 10 mL) at ice-water and stirred at r.t. for 2 hours. The reaction mixture was quenched by adding water, and then filtrated. The filtrate cake was collected and dried under vacuo to give I-i Oa (2.0 g) ESI-MS (Mi-i): 411 calc. for C17H19C1N404S: 410.1.Preparation of intermediate 1-10a: 4-Ethoxy-3-(6, 7-dihvdro-1 -methyl-7-oxo-3- propyl-1 H-pyrazolo[4, 3-c lpyrimidin-5-yl)benzene-1 -sulfonyl chloride l-09a (2.5 g, 8.0 mmol) was added into CISO

Sildenafil derivative

Molecular Weight:410.9
XLogP3:2.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:6
Exact Mass:410.0815540
Monoisotopic Mass:410.0815540
Topological Polar Surface Area:111
Heavy Atom Count:27
Complexity:696
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes