With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.873397-34-3,Tetrahydro-2H-pyran-3-carboxylic acid,as a common compound, the synthetic route is as follows.
To a 50-mL round-bottom flask was added 2-(pyridin-2-ylsulfonyl)-1,2,3,4,5,6- hexahydropyrrolo[3,4-c]pyrrole (100 mg, 0.40 mmol, 1.00 equiv), oxane-3-carboxylic acid (52 mg, 0.40 mmol, 1.00 equiv), HATU (302 mg, 0.79 mmol, 1.97 equiv), DCM (10 mL), and DIEA (154 mg, 1.19 mmol, 2.99 equiv). The solution was stirred overnight at 20 ¡ãC. The mixture was diluted with 20 mL of DCM, washed with 2×20 mL of water, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by silica gel column chromatography, eluting with ethyl acetate/petroleum ether (10/1). The enantiomers were separated by prep-Chiral HPLC with the following conditions: column, Daicel CHIRALPAK ^ IA 21.2 ^ 250 mm, 5 mum; mobile phase, A = Hexane, phase B = EtOH (hold 50.0percent EtOH over 42 min); flow rate, 20 mL/min; Detector, UV 254 & 220 nm. Absolute stereochemistry was not determined (*). This provided: Example 44. (R or S)-(5-(pyridin-2-ylsulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)(tetrahydro-2H-pyran-3-yl)methanone (stereochemical configuration assumed). Isolated as a white solid (12.1 mg, 8percent). Prep-Chiral HPLC Rt = 24.472 min. 1H NMR (400 MHz, CDCl3): delta 8.73-8.69 (m, 1H), 8.03-7.88 (m, 2H), 7.56-7.42 (m, 1H), 4.43-4.26 (m, 6H), 4.16 (d, J = 3.6 Hz, 2H), 3.98-3.87 (m, 2H), 3.54 (t, J = 12.0 Hz, 1H), 3.50-3.34 (m, 1H), 2.68-2.49 (m, 1H), 1.96-1.76 (m, 2H), 1.69-1.48 (m, 2H). LCMS: m/z = 364.0 [M+H]+. Example 45. (S or R)-(5-(pyridin-2-ylsulfonyl)-3,4,5,6-tetrahydropyrrolo[3,4- c]pyrrol-2(1H)-yl)(tetrahydro-2H-pyran-3-yl)methanone (stereochemical configuration assumed). Isolated as a white solid (7.3 mg, 5percent). Prep-Chiral HPLC Rt = 33.498 min. 1H NMR (400 MHz, CDCl3): delta 8.75-8.67 (m, 1H), 8.04-7.88 (m, 2H), 7.58-7.39 (m, 1H), 4.43-4.26 (m, 6H), 4.18-4.16 (m, 2H), 4.00-3.89 (m, 2H), 3.54 (t, J = 12.0 Hz, 1H), 3.48-3.29 (m, 1H), 2.69-2.48 (m, 1H), 1.95-1.76 (m, 2H), 1.72-1.58 (m, 2H). LCMS: m/z = 364.2 [M+H]+.
As the paragraph descriping shows that 873397-34-3 is playing an increasingly important role.
Reference£º
Patent; FORMA THERAPEUTICS, INC.; ERICSSON, Anna; GREEN, Neal; GUSTAFSON, Gary; HAN, Bingsong; LANCIA, JR., David R.; MITCHELL, Lorna; RICHARD, David; SHELEKHIN, Tatiana; SMITH, Chase C.; WANG, Zhongguo; ZHENG, Xiaozhang; (140 pag.)WO2018/175474; (2018); A1;,
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