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【结 构 式】

【分子编号】16547

【品名】(1-[[(methylsulfonyl)oxy]methyl]cyclopropyl)methyl benzoate

【CA登记号】

【 分 子 式 】C13H16O5S

【 分 子 量 】284.33304

【元素组成】C 54.92% H 5.67% O 28.13% S 11.28%

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:(XXV)

Compound (XIX) is condensed with 2-[1-(acetylsulfanylmethyl)cyclopropyl]acetic acid methyl ester (XX) by means of Cs2CO3 in acetonitrile yielding the expected condensation product (XXI). Finally, this compound is treated successively with pyridine and p-toluenesulfonic acid to eliminate the tetrahydropyranyl protecting group, and with NaOH to hydrolyzed the acetate ester group of (XXI). 4) The 2-[1-(acetylsulfanylmethyl)cyclopropyl]acetic acid methyl ester (XX) has been obtained as follows: The reduction of diethyl cyclopropane-1,1-dicarboxylate (XXII) with LiAlH4 in THF gives 1,1-cyclopropanedimethanol (XI), which is monobenzoylated with benzoyl chloride (XXIII) and pyridine in dichloromethane yielding benzoic acid 1-(hydroxymethyl)cyclopropylmethyl ester (XXIV). The mesylation of (XXIV) as usual affords the mesylate (XXV), which is treated with NaCN in DMSO to give 2-[1-(benzoyloxymethyl)cyclopropyl]acetonitrile (XXVI). The hydrolysis of (XXVI) with KOH in refluxing ethanol, followed by methylation with diazomethane, yields methyl 2-[1-(hydroxymethyl)cyclopropyl]acetate (XXVII), which is mesylated as usual affording the mesylate (XXIII). Finally, this compound is treated with cesium thiocetate in dichloromethane to give (XX).

1 Graul, A.; Martín, L.; Castañer, J.; Montelukast Sodium. Drugs Fut 1997, 22, 10, 1103.
2 Labelle, M.; Belley, M.; Gareau, Y.; et al.; Discovery of MK-0476, a potent and orally active leukotriene D4 receptor antagonist devoid of peroxisomal enzyme induction. Bioorg Med Chem Lett 1995, 5, 3, 283-8.
3 Belley, M.L.; Leger, S.; Roy, P.; Xiang, Y.B.; Labelle, M.; Guay, D. (Merck Frosst Canada Inc.); Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists. EP 0480717; JP 1993105665 .
4 Bhupathy, M.; McNamara, J.M.; Sidler, D.R.; Volante, R.P.; Bergan, J.J. (Merck & Co., Inc.); Process for the preparation of leukotriene antagonists. WO 9518107 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XI) 16533 [1-(hydroxymethyl)cyclopropyl]methanol C5H10O2 详情 详情
(XVIII) 16540 (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]-1-propanol C34H36ClNO3 详情 详情
(XIX) 16541 (1S)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl methanesulfonate C35H38ClNO5S 详情 详情
(XX) 16542 methyl 2-[1-[(acetylsulfanyl)methyl]cyclopropyl]acetate C9H14O3S 详情 详情
(XXI) 16543 methyl 2-(1-[[((1R)-1-[3-[(E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-[1-methyl-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]phenyl]propyl)sulfanyl]methyl]cyclopropyl)acetate C41H46ClNO4S 详情 详情
(XXII) 16544 diethyl 1,1-cyclopropanedicarboxylate 1559-02-0 C9H14O4 详情 详情
(XXIII) 10463 Benzoyl chloride 98-88-4 C7H5ClO 详情 详情
(XXIV) 16546 [1-(hydroxymethyl)cyclopropyl]methyl benzoate C12H14O3 详情 详情
(XXV) 16547 (1-[[(methylsulfonyl)oxy]methyl]cyclopropyl)methyl benzoate C13H16O5S 详情 详情
(XXVI) 16548 [1-(cyanomethyl)cyclopropyl]methyl benzoate C13H13NO2 详情 详情
(XXVII) 16549 methyl 2-[1-(hydroxymethyl)cyclopropyl]acetate C7H12O3 详情 详情
Extended Information