4-CHLORO-1-(3,5-DIMETHYLPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDINE synthesis

Yield:885524-15-2 86.6%

Reaction Conditions:

with trichlorophosphate at 105 - 108;Inert atmosphere;

Steps:

7e

Example-7ePreparation of 4-chloro-1-(3,5-dimethyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine (Compound No: 79) 650.0 g of Phosphorus (V) oxychloride (POCl3) was charged into a 2.0 L 4 necked round bottom flask connected to a mechanical stirrer, thermo meter socket, and condenser under nitrogen atmosphere. 60.0 g (0.25 mol) of 1-(3,5-Dimethyl-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidine-4-one (Compound No. 78) was charged. Reaction mass temperature was raised to reflux (105-108° C.). Maintained the mass temperature at reflux for 8-9 hour's. Reaction mass temperature was cooled to 25-30° C. and 600.0 ml of chloroform was charged. Maintained the mass temperature at 25-30° C. for 30-45 min. 2.0 kg's of crushed ice was charged into a 5.0 L 4 necked round bottom flask connect to a mechanical stirrer, thermo meter socket, and condenser. Reaction mass was added slowly at maintaining the mass temperature below 10° C. Maintained the mass temperature at 0-10° C. for 30-45 min. Mass temperature was raised to 25-30° C. 600.0 ml of Chloroform was charged. Maintained the mass temperature at 25-30° C. for 30-45 min and settled the mass for 20-30 min. Separated the bottom organic layer. Organic layer was dried with sodium sulphate upto obtaining the moisture content is not more than 0.20% w/v. 15.0 g of carbon was charged. Mass temperature was raised to 45-50° C. Maintained the mass temperature at 45-50° C. for 30-45 min. Carbon and sodium sulphate was filtered through hyflow bed and bed was washed with 300.0 ml of chloroform. Filtrate was collected into a flask. Chloroform was distilled completely under vacuum at mass temperature not crossing 60° C. Finally applied high vacuum to complete remove the traces of chloroform at mass temperature not crossing 60° C. Mass temperature was cooled to 25-30° C. and release the vacuum. 250.0 ml of isopropyl ether was charged. Maintained the mass temperature at 25-30° C. for 45-60 min. Solid was filtered and the solid was washed with 50.0 ml of isopropyl ether. Compound was dried under vacuum at 55-60° C. Dry weight of the compound: 56.0 g (yield 86.6%).Product purity by HPLC-99.79%.Spectral data:FT-IR (K Br) (cm-¹): 3096, 2952, 2913, 2854, 1614, 1605, 1589, 1546, 1481, 1426, 13791351, 1274,1261, 1225, 848, 640,400 MHz ₁H NMR (DMSO-d₆): δ value (ppm): 2.36 s (CH3), 2.49 s (CH3), 7.05 s [Ar-Ha, Hb (2H)], 7.73 s [Ar-Hc (1H)], 8.69 s (1H), 8.95 s (1H)¹³C NMR: δ value (ppm): 20.97(2C), 114.47(1C), 118.62(2C), 128.56(1C), 133.52(2C), 137.70(1C), 138.56(1C), 152.33(1C), 154.0(1C), 155.2(1C)MS: 259.26[M+1], 223.28[M-Cl]

References:

US2010/298351,2010,A1 Location in patent:Page/Page column 33-34