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【结 构 式】

【分子编号】57848

【品名】5-(chloromethyl)-3,4-diphenyl-4,5-dihydro-5-isoxazolol

【CA登记号】

【 分 子 式 】C16H14ClNO2

【 分 子 量 】287.7454

【元素组成】C 66.79% H 4.9% Cl 12.32% N 4.87% O 11.12%

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:(IV)

Treatment of deoxybenzoin (I) with hydroxylamine hydrochloride produces the corresponding oxime (II). Condensation of the dilithium derivative of (II) with methyl chloroacetate (III) generates the dihydroisoxazole (IV). Subsequent chlorosulfonation of (IV), followed by treatment with ammonia, furnishes sulfonamide (V). Then, displacement of the chloro group of (V) with silver nitrate gives rise to the target nitrate ester. Alternatively, chloride (V) is converted to alcohol (VI) by displacement with formic acid, followed by alkaline hydrolysis. Then, reaction of alcohol (VI) with in situ generated acetyl nitrate yields the corresponding nitrate.

1 Schroeder, J.D.; et al.; NMI-1093: A nitric oxide-enhanced cyclooxygenase-2 selective inhibitor with cardioprotective potential. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 316.
2 Garvey, D.S.; Tam, S.W.; Letts, L.G.; Schroeder, J.D.; Bandarage, U.K.; Fang, X.; Bandarage, R.R. (NitroMed Inc.); Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compsns. and methods of use. WO 0145703 .
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) 41003 1,2-diphenyl-1-ethanone; Deoxybenzoin-2-phenylacetophenone; Dexybenzoin 451-40-1 C14H12O 详情 详情
(II) 41004 1,2-diphenyl-1-ethanone oxime C14H13NO 详情 详情
(III) 10257 methyl 2-chloroacetate; methyl chloroacetate 96-34-4 C3H5ClO2 详情 详情
(IV) 57848 5-(chloromethyl)-3,4-diphenyl-4,5-dihydro-5-isoxazolol C16H14ClNO2 详情 详情
(V) 57849 4-[5-(chloromethyl)-3-phenyl-4-isoxazolyl]benzenesulfonamide C16H13ClN2O3S 详情 详情
(VI) 57850 4-[5-(hydroxymethyl)-3-phenyl-4-isoxazolyl]benzenesulfonamide C16H14N2O4S 详情 详情
Extended Information