Dichlorophosphoric acid 2-bromoethyl ester -Drug Synthesis Database

【结构式】

【分子编号】13033

【品名】Dichlorophosphoric acid 2-bromoethyl ester

【CA登记号】

【分子式】C₂H₄BrCl₂O₂P

【分子量】241.835722

【元素组成】C 9.93% H 1.67% Br 33.04% Cl 29.32% O 13.23% P 12.81%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(VI)

Two different routes have been described for the preparation of Et-18-OCH3: 1) The methylation of 1,3-benzylideneglycerol (I) with methyl iodide and KOH gives 1,3-benzytidene-2-O-methylglycerol (II), which is hydrolyzed with HCl to 2-O-methylglycerol (III). The condensation of (III) with octadecyl bromide (IV) and KOH in DMSO/THF yields 1-O-octadecyl-2-O-methyl-(rac)-glycerol (V), which by reaction with phosphorodichloric acid 2-bromoethyl ester (VI) and pyridine is converted to 3-octadecyloxy-2-methoxypropyl bromoethyl phosphate (VII). Finally, this compound is converted to Et-18-OCH3 with trimethylamine (VIII) in toluene and treated with silver carbonate to remove traces of bromide. 2) The reaction of 1,2-isopropylidene-sn-glycerol (IX) with benzyl bromide (X) and NaNH2 in benzene gives 1,2-isopropylidene-3-O-benzyl-sn-glycerol (XI), which is hydrolyzed with acetic acid to 3-O-benzyl-sn-glycerol (XII). The etherification of (XII) with (IV) as before or with NaNH2 gives 1-O-octadecyl-3-O-benzyl-sn-glycerol (XIII), which is methylated with methyl iodide and NaNH2 in dioxane to give 1-O-octadecyl-2-O-methyl-3-O-benzyl-sn-glycerol (XIV). Finally, this compound is debenzytaled by hydrogenolysis with H2 over Pd/C in petroleum ether to form (V), an intermediate previously described above.

参考文献中间体

合成目标

【1】 Tsutsumi, H.; Kamata, T.; Nakajima, K.; Katagi, M.; Tsuchihashi, H.; Nishioka, H.; Nishikawa, M.; Miki, A.; Tatsuno, M.; Chem Phys Lipids 1982, 30, 9, 389-392.
【2】 Fast, L.D.; et al.; Chem Pharm Bull 1982, 30, 9, 3260-3270.
【3】 Castaner, R.M.; Castaner, J.; Serradell, M.N.; ET-18-OCH3. Drugs Fut 1987, 12, 4, 341.

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)	28795	2-phenyl-1,3-dioxan-5-ol	1708-40-3	C₁₀H₁₂O₃	详情	详情
(II)	28796	5-methoxy-2-phenyl-1,3-dioxane		C₁₁H₁₄O₃	详情	详情
(III)	13579	2-Methoxy-1,3-propanediol		C₄H₁₀O₃	详情	详情
(IV)	28797	1-bromooctadecane	112-89-0	C₁₈H₃₇Br	详情	详情
(V)	28798	2-methoxy-3-(octadecyloxy)-1-propanol		C₂₂H₄₆O₃	详情	详情
(VI)	13033	Dichlorophosphoric acid 2-bromoethyl ester		C₂H₄BrCl₂O₂P	详情	详情
(VII)	28799	2-bromoethyl 2-methoxy-3-(octadecyloxy)propyl hydrogen phosphate		C₂₄H₅₀BrO₆P	详情	详情
(IX)	16476	2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane; (2,2-dimethyl-1,3-dioxolan-4-yl)methanol; 2,3-o-Isopropylideneglycerol	100-79-8	C₆H₁₂O₃	详情	详情
(X)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(XI)	28800	benzyl 2,2-dimethyl-1,3-dioxolan-4-yl ether		C₁₂H₁₆O₃	详情	详情
(XII)	28801	1-(benzyloxy)-1,2-ethanediol		C₉H₁₂O₃	详情	详情
(XIII)	28802	1-(benzyloxy)-2-(octadecyloxy)-1-ethanol		C₂₇H₄₈O₃	详情	详情
(XIV)	28803	1-[[1-methoxy-2-(octadecyloxy)ethoxy]methyl]benzene		C₂₈H₅₀O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of 2-methoxypropane-1,3-diol (I) with octadecylisocyanate (II) in pyridine gives 3-(N-octadecylcarbamoyloxy)-2-methylpropanol (III), which is esterified with 2-bromoethyl phosphorodichloridate (IV) by means of pyridine in benzene and treated with water to afford 3-(N octadecyicarbamoyloxy)-2-methoxypropyl2-bromoethyl acid phosphate (V). Finally, this compound is treated with thiazole (VI) and Ag2CO3 in hot toluene.

参考文献中间体

合成目标

【1】 Inada, Y.; Terashita, Z.; Yoshioka, Y.; Tsushima, S.; Nishikawa, K.; Nomura, H.; CV-3988 - A specific antagonist of platelet activa. Life Sci 1983, 32, 1975.
【2】 Nomura, H.; Hozumi, M.; Yoshioka, Y. (Takeda Chemical Industries, Ltd.); Carbamic acid esters, their production and use. EP 0035375 .
【3】 Castaner, J.; Prous, J.; CV-3988. Drugs Fut 1987, 12, 1, 12.

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)	13579	2-Methoxy-1,3-propanediol		C₄H₁₀O₃	详情	详情
(II)	13586	1-Isocyanatooctadecane; octadecyl isocyanate	112-96-9	C₁₉H₃₇NO	详情	详情
(III)	22997	3-hydroxy-2-methoxypropyl octadecylcarbamate		C₂₃H₄₇NO₄	详情	详情
(IV)	13033	Dichlorophosphoric acid 2-bromoethyl ester		C₂H₄BrCl₂O₂P	详情	详情
(V)	22999	3-[[(2-bromoethoxy)(hydroxy)phosphoryl]oxy]-2-methoxypropyl octadecylcarbamate		C₂₅H₅₁BrNO₇P	详情	详情
(VI)	23000	1,3-thiazole	288-47-1	C₃H₃NS	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

The reaction of 2'-deoxy-5-fluoro-3'-O-oleoyluridine (I) with 2-bromoethylphosphodichloridate (II) by means of lutidine in THF gives 2'-deoxy-5-fluoro-3'-O-oleoyluridine 5'-(2-bromoethyl)phosphate (III), which is then condensed with trimethylamine (IV) in toluene.

参考文献中间体

合成目标

【1】 Hori, T.; Myokan, I.; Miyabara, S. (Toyama Chemical Co., Ltd.); Novel 5-fluro-2'-desoxyuridine derivs. and their salts, process for their preparation and antitumor compsns. containing them. CH 670091; DE 3535766; FR 2571374; GB 2166740; JP 1986171498; US 4684631; US 4740503 .
【2】 Hoshi, A.; Prous, J.; Castaner, J.; T-506. Drugs Fut 1990, 15, 5, 467.

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)	13032	(2R,3S,5R)-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2-(hydroxymethyl)tetrahydro-3-furanyl (Z)-9-octadecenoate		C₂₇H₄₃FN₂O₆	详情	详情
(II)	13033	Dichlorophosphoric acid 2-bromoethyl ester		C₂H₄BrCl₂O₂P	详情	详情
(III)	13034	(2-bromoethoxy)([(2R,3S,5R)-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-3-[(Z)-9-octadecenoyloxy]tetrahydro-2-furanyl]methoxy)oxophosphoranolate		C₂₉H₄₆BrFN₂O₉P	详情	详情
(IV)	13035	N,N,N-Trimethylamine; Trimethyl amine; N,N-Dimethylmethanamine	75-50-3	C₃H₉N	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The intermediate N,N,N',N'-tetrakis(2-chloroethyl)phosphorodiamidate (IV) was prepared by an improved procedure consisting of addition of phosphoryl chloride to 2-bromoethanol (I) in the presence of Et3N, followed by in situ treatment of the resulting intermediate (II) with bis(2-chloroethyl)amine (III).

参考文献中间体

合成目标

【1】 Lyttle, M.H.; et al.; Glutathione-S-transferase activates novel alkylating agents. J Med Chem 1994, 37, 10, 1501.
【2】 Kauvar, L.; Lyttle, M.H.; Satyam, A. (Telik, Inc.); Glutathione S-transferase-activated cpds.. WO 9509866 .

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)	10059	Ethylene bromohydrin; 2-Bromo-1-ethanol	540-51-2	C₂H₅BrO	详情	详情
(II)	13033	Dichlorophosphoric acid 2-bromoethyl ester		C₂H₄BrCl₂O₂P	详情	详情
(III)	21583	2-chloro-N-(2-chloroethyl)-1-ethanamine; Bis(2-chloroethyl)amine; 1,1'-iminobis(2-chloroethane); N,N-bis(2-chloroethyl)amine	821-48-7	C₄H₉Cl₂N	详情	详情
(IV)	46425			C₁₀H₂₀BrCl₄N₂O₂P	详情	详情

Extended Information