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【结 构 式】

【分子编号】56719

【品名】2-({(1R)-1-[2-(2,4-difluorophenyl)-2-oxiranyl]ethyl}oxy)tetrahydro-2H-pyran; (1R)-1-[2-(2,4-difluorophenyl)-2-oxiranyl]ethyl tetrahydro-2H-pyran-2-yl ether

【CA登记号】

【 分 子 式 】C15H18F2O3

【 分 子 量 】284.3029264

【元素组成】C 63.37% H 6.38% F 13.36% O 16.88%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VIII)

The condensation of (R)-lactic acid (I) with morpholine (II) gives the corresponding morpholide (III), which is protected at the hydroxyl position with dihydropyran (IV) to yield the tetrahydropyranyl ether (V). The Grignard reaction of (V) with 2,4-difluorophenylmagnesium bromide (VI) affords the chiral 1-propanone (VII), which by a Corey's diastereoselective epoxidation with trimethylsulfoxonium iodide is converted into the oxirane (VIII). The opening of the oxirane ring of (VIII) by means of 1,2,4-triazole (IX) and NaH provides the tertiary alcohol (X), which is treated with pyridine p-toluenesulfonate to give the deprotected diol (XI) as a (2R,3R) and (2R,3S) 4:1 diastereomeric mixture, from which the desired (2R,3R)-isomer (XII) was isolated by crystallization. The reaction of (XII) with Ms-Cl and TEA, followed by cyclization with NaOMe, yields the oxirane (XIII), which is finally condensed with 7-chloroquinazolin-4(3H)-one (XIV) by means of K2CO3 in hot NMP.

1 Tasaka, A.; Tamura, N.; Matsushita, Y.; Teranishi, K.; Hayashi, R.; Okonogi, K.; Itoh, K.; Optically active antifungal azoles. I. Synthesis and antifungal activity of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol and stereoisomers. Chem Pharm Bull 1993, 41, 6, 1035-42.
2 Bartroli Orpi, J.; Anguita Lopez, M. (J. Uriach & Cia., SA); Method for preparing pyrimidone derivs. with antifungal activity. ES 2159488; WO 0166519 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 11591 methyl (2R)-2-hydroxypropanoate 17392-83-5 C4H8O3 详情 详情
(II) 10388 Morpholine 110-91-8 C4H9NO 详情 详情
(III) 56718 (2R)-2-hydroxy-1-(4-morpholinyl)-1-propanone C7H13NO3 详情 详情
(IV) 13684 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran 110-87-2 C5H8O 详情 详情
(V) 45574 (2R)-1-(4-morpholinyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone C12H21NO4 详情 详情
(VI) 20262 bromo(2,4-difluorophenyl)magnesium C6H3BrF2Mg 详情 详情
(VII) 56717 (2S)-1-(2,4-difluorophenyl)-2-methyl-3-tetrahydro-2H-pyran-2-yl-1-propanone C15H18F2O2 详情 详情
(VIII) 56719 2-({(1R)-1-[2-(2,4-difluorophenyl)-2-oxiranyl]ethyl}oxy)tetrahydro-2H-pyran; (1R)-1-[2-(2,4-difluorophenyl)-2-oxiranyl]ethyl tetrahydro-2H-pyran-2-yl ether C15H18F2O3 详情 详情
(IX) 13135 1H-1,2,4-Triazole; 1,2,4-Triazole 288-88-0 C2H3N3 详情 详情
(X) 56720 (3R)-2-(2,4-difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)-1-(1H-1,2,4-triazol-1-yl)-2-butanol C17H21F2N3O3 详情 详情
(XI) 56721 (3R)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol C12H13F2N3O2 详情 详情
(XII) 13106 (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol C12H13F2N3O2 详情 详情
(XIII) 31738 1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole C12H11F2N3O 详情 详情
(XIV) 50077 7-chloro-4(3H)-quinazolinone C8H5ClN2O 详情 详情
Extended Information