Reference of 50270-27-4, With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.50270-27-4, name is 2,4,6-Trichloropyrimidine-5-carbaldehyde, molecular formula is C5HCl3N2O, molecular weight is 211.4332, as common compound, the synthetic route is as follows.
N-{4-[1-(1-benzylpiperidin-4-yl)-4-(3,6-dihydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}acetamide (Scheme 6)Example 3To a solution of 2,4,6-trichloro-pyrimidine-5-carbaldehyde (1.53 g, 7.19 mmol) in anhydrous ethanol (25 mL) at -78° C. was added (1-benzyl-piperidin-4-yl)-hydrazine hydrochloride (2 g, 7.19 mmol) and triethylamine (5.01 mL). After 30 min allow the reaction mixture to warm to 0° C. After 1 h warm to 25° C. Add ethyl acetate and extract with saturated aqueous sodium bicarbonate, water (2.x.) and brine. Dry over anhydrous magnesium sulfate. Concentrate in vacuo to give an oil. Add diethyl ether and remove precipitate by filtration. Concentrate mother liquor and add diethyl ether and remove precipitate by filtration. Add 2N HCl in diethyl ether to mother liquor and collect the precipitate. 1-(1-Benzyl-piperidin-4-yl)-4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine hydrochloride is obtained as a white solid is obtained. A mixture of this white solid (530 mg, 1.34 mmol), tributyl-(3,6-dihydro-2H-pyran-4-yl)-stannane (500 mg), PdCl2(PPh3)2 (50 mg), diisopropylethyl amine (230 muL) in dimethylformamide (6 mL) is heated to 70° C. After 3 h at 70° C. and 18 h at 60° C.° the dimethylformamide is removed in vacuo. The residue is dissolved in dichloromethane and washed with saturated aqueous sodium bicarbonate. The organic phase is dried over anhydrous magnesium sulfate and concentrated in vacuo to give a dark oil. The oil is treated with 4-acetamidophenylboronic acid (72 mg, 0.402 mmol), Pd(PPh3)4 (5 mg) and 2M aqueous sodium carbonate (0.281 mL, 0.563 mmol) in dimethoxyethane (1 mL) and heated in a microwave at 175° C. for 15 min. The reaction mixture is purified by reverse phase HPLC (CH3CN/H2O/CF3CO2H) followed by silica gel chromatography (CH2Cl2/MeOH) to give the title compound as a trifluoroacetate salt (7.7 mg).
The chemical industry reduces the impact on the environment during synthesis 50270-27-4, I believe this compound will play a more active role in future production and life.
Reference:
Patent; Wyeth; US2009/192176; (2009); A1;,
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia