With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.103260-44-2,Ethyl 2-(tetrahydro-2H-pyran-4-yl)acetate,as a common compound, the synthetic route is as follows.
General procedure: 5.1.5 2-[4-({[4-(1,4-Dioxaspiro[4.5]dec-8-yl)-1-methyl-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline (6a) To a stirred mixture of lithium bis(trimethylsilyl)amide (1 M solution in THF, 30.1 mL, 30.1 mmol) in THF (45 mL) cooled with dry ice-acetone bath were dropwisely added a solution of ethyl 1,4-dioxaspiro[4.5]dec-8-ylacetate (5a, 6.55 g, 28.7 mmol) with keeping the temperature below -65 C, and the mixture was stirred at the same temperature for 50 min. To the resultant mixture was dropwisely added methyl formate (3.45 g, 57.4 mmol) with keeping the temperature below -65 C, and the mixture was stirred at the same temperature for 10 min. The resultant mixture was allowed to warm up to room temperature and stirred for 3 h. The reaction was cooled with ice-water bath and quenched with ca. 40 mL of 1 M HCl aqueous solution. The mixture was diluted with brine and extracted with CHCl3, The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give an orange oil. To this orange oil in EtOH (59 mL) was added methylhydrazine (2.64 g, 57.4 mmol), and the mixture was stirred at 100 C for 3 h before cooling at room temperature. The mixture was concentrated in vacuo, and the residue was purified by silica gel column chromatography (0-15% MeOH in CHCl3) to give a white solid (2.91 g). To this white solid (1.48 g) and 2-[4-(chloromethyl)phenyl]quinoline hydrochloride (1.8 g, 6.20 mmol) in DMF (18 mL) was added K2CO3 (2.14 g, 15.5 mmol), and the mixture was stirred at 60 C for 1 h before cooling at room temperature. The mixture was diluted with water and brine, and the mixture was extracted with CHCl3/MeOH (5:1) for 3 times. The combined organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (0-3% MeOH in CHCl3) to give 6a (1.10 g, 17%) as a pale yellow oil. 5.1.6 2-[4-({[1-Methyl-4-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]quinoline hydrochloride (6b) Free form of title compound was prepared from 5b in a manner similar to that described for compound 6a, with a yield of 25% as a colorless oil. To this colorless oil (139 mg, 0.35 mmol) in EtOAc (9.7 mL) was added 4 M HCl/EtOAc (0.174 mL), and the mixture was stirred at room temperature for 1 h. The precipitate was collected by filtration to give 6b (76 mg, 50%) as a beige solid.
The synthetic route of 103260-44-2 has been constantly updated, and we look forward to future research findings.
Reference£º
Article; Hamaguchi, Wataru; Masuda, Naoyuki; Miyamoto, Satoshi; Shiina, Yasuhiro; Kikuchi, Shigetoshi; Mihara, Takuma; Moriguchi, Hiroyuki; Fushiki, Hiroshi; Murakami, Yoshihiro; Amano, Yasushi; Honbou, Kazuya; Hattori, Kouji; Bioorganic and Medicinal Chemistry; vol. 23; 2; (2015); p. 297 – 313;,
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