154127-42-1 A common heterocyclic compound, 154127-42-1,(S)-4-Hydroxy-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e][1,2]thiazine-6-sulfonamide 1,1-dioxide, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Compound B (50.0 g, 140.7 mmol) was added to 450 mL of acetonitrile, trimethyl orthoacetate (27.0 g, 225.1 mmol) and triethylamine (1.4 g, 14.0 mmol) were added with stirring, and the mixture was heated to 78C. , stirring for 5h,HPLC monitoring showed complete reaction and the HPLC monitoring results are shown in Table 1 (see FIG. 1).Cool to 40C, distill off under reduced pressure, and concentrate to a minimum volume.Compound C crude product was obtained.The crude compound C was dissolved in 180 mL of tetrahydrofuran, cooled to -10 DEG C, triethylamine (31.3 g, 309.5 mmol) was slowly added dropwise at a drip rate of 1 d/s, and the addition was completed at a drip rate of 3 d/s. 4- A solution of tosyl chloride (53.5 g, 280.6 mmol) in 70 mL of tetrahydrofuran. After the addition, the temperature was controlled at -4C, and the reaction was complete after about 3 hours.At a controlled temperature of 10 C. or less, a 70% aqueous solution of ethylamine (361.0 g, 5.6 M) was slowly added dropwise at a rate of 5 d/s. After the addition, the temperature was kept stirring at 12C and the reaction was complete after about 15 hours.The mixture was concentrated under reduced pressure to 70-80 mL, and the temperature was lowered to 0C. The temperature was controlled below 30C, and concentrated hydrochloric acid (12 mol/L) was added dropwise to adjust the pH to 1 to 2, and then about 14 mL of concentrated hydrochloric acid (12 mol/L) was added. The mixture was stirred at room temperature for 1 hour. The reaction was extracted twice with methyl tert-butyl ether (2*250 mL). The organic phases were combined and extracted once with dilute hydrochloric acid (1 mol/L, 100 mL). Combine the aqueous phases, slowly add sodium bicarbonate solids, adjust the pH to 5-6, add 150 mL of water, and adjust the pH to 7-8 with 7% sodium bicarbonate solution. After adjustment, stir at room temperature for 15 h and slowly crystallize. After filtration, the filter cake was rinsed with 30 mL of water and the cake was dried to obtain 35.4 g of product with a purity of 98.3%.Add 250 mL of dichloromethane, 25 mL of methanol to the filter mother liquor, stir, extract, separate, and concentrate the organic phase to dryness4.6 g of yellow viscous material was added and 10 mL of ethyl acetate was added. Heat to 70 ~ 75 C dissolved, slowly dropped to 0 ~ 10 C, stirring 1 ~ 2h, precipitation of a white solid, continue stirring 3 ~ 4h, filtration, with 3mL water filter cake, filter cake drying,Obtained product 2.4g, purity 97.3%.Combined, the purity was 98.1%, the total yield was 65.3%, the ignition residue was 0.08%, and the chiral purity was 99.7%.
Chemical properties determine the actual use. Each compound has specific chemical properties and uses. We look forward to more synthetic routes in the future to expand 154127-42-1 reaction routes.
Reference£º
Patent; Shandong Weizhi Pharmaceutical Co., Ltd.; Shanghai Weizhi Pharmaceutical Technology Co., Ltd.; Wang Jianhua; He Yigang; Wei Yanjun; Xing Yanping; Zhao Tianchang; (27 pag.)CN107759618; (2018); A;,
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