* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With potassium iodide; sodium hydroxide; In ethanol; at 15 - 55℃; for 0.5h;Inert atmosphere; Large scale;
(1) Add 102.0 kg of 95% ethanol to a 200 L reactor, and add 6.2 kg of pharmaceutically acceptable hydroxide under nitrogen protection.Sodium, stirred and dissolved. The temperature of the reaction solution was controlled at 15 to 25 C, and 11.9 kg of 2-mercapto-5-methoxybenzimidazole, 15.0 kg of Omega chloride (ie 67.87 mol) and 0.3 kg of potassium iodide were sequentially added.Slowly raise the temperature to 50 C -55 C, keep the reaction for 30 minutes;(wherein the molar ratio of 2-mercapto-5-methoxybenzimidazole, Omega chloride, sodium hydroxide and potassium iodide is 1:1.02: 2.27: 0.027; 95% ethanol is 7 times the mass of Omega chloride, or 2-mercapto-5-methoxybenzimidazole8.8 times the quality).(2) Sampling was monitored by TLC method (developing agent ethyl acetate: n-hexane = 1:1) 2-mercapto-5-methoxybenzoThe imidazole spots disappeared and the reaction was terminated and post-treatment; if 2-mercapto-5-methoxybenzimidazole spots were still visible, the reaction was continued and samples were taken every 15 minutes for monitoring until the spots disappeared.(3) Concentrated under reduced pressure at 45 to 50 C to remove ethanol. 83.3 kg of ice water was added to the residue, and the pH was adjusted to about 7 with hydrochloric acid, wherein the amount of ice water added was 5.55 times the mass of Ogilvy & Mather.(4) 30 kg of dichloromethane was added, stirred for 15 minutes, and the layers were allowed to stand, and the dichloromethane layer was separated; the aqueous layer was extracted three times with dichloromethane (16.7 kg*3 each time).The methylene chloride phase was combined, and the purified water was washed twice (33.3 kg*2), and washed with saturated brine.It was dried twice (32.5 kg * 2) and 10 kg of anhydrous sodium sulfate for 2 hours. Filtration and concentration of the filtrate under reduced pressure gave 21.62 kg of intermediate 1 (ie, containing omeprazole sulphide 64.54 mol, as shown in the purity of 98.383% (see Figure 1).Light yellow viscous). The yield was 64.54 / 67.87 = 95.1%.
With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; for 20h;Combinatorial reaction / High throughput screening (HTS);
Each resin from Step 3 was distributed into 24 fritted syringes (Torvig, 50 mg each, 50 mumol), for a total of 96 syringes, and was swelled in NMP (1 mL) for 30 min. The solvent was removed by filtration. Twenty-four solutions of the building blocks listed below (10 mmol each) and DIBA (3.5 mL, 20 mmol) in NMP (10 mL) were prepared. 3 mL of the 24 solutions was added to the 24 syringes for each resin from Step 3, accordingly. The suspensions were then shaken for 20 h on a Titer Plate Shaker. The reaction mixture was filtered and washed 5 times with methylene chloride (5 mL), 3 times with THF (5 mL), 3 times THF/H2O (3/1 v/v, 5 mL), and 3 times with THF (5 mL). The resins were then dried overnight under vacuum.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
