1-Isocyanatooctadecane; octadecyl isocyanate -Drug Synthesis Database

【结构式】

【分子编号】13586

【品名】1-Isocyanatooctadecane; octadecyl isocyanate

【CA登记号】112-96-9

【分子式】C₁₉H₃₇NO

【分子量】295.50892

【元素组成】C 77.23% H 12.62% N 4.74% O 5.41%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

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2

该中间体在本合成路线中的序号：(VIII)

The racemic form of E-5880 is prepared as follows: The esterification of 2-methoxy-1,3-propanediol (I) with phenyl chlorocarbonate (II) in pyridine gives the diester (III), which is treated with 2-(aminomethyl)pyridine (IV) in refluxing chloroform, yielding the carbamate (V). The reaction of (V) with 4-hydroxypiperidine (VI) in refluxing chloroform affords the dicarbamate (VII), which by treatment with octadecyl isocyanate (VIII) gives the tricarbamate (X). Alternatively, (X) can be obtained by treatment of (VIII) with carbonate (II), yielding the intermediate (IX), which by treatment with octadecylamine (XI) at 100 C affords (X). The acylation of (X) with 2-methoxybenzoyl chloride (XII) in pyridine gives the precursor (XIII), which is finally treated with ethyl iodide in excess at reflux temperature and submitted to an ion exchange resin (Amberlite IRA-410 Cl- type). The optically active (R)-enantiomer is synthesized starting from L-mannitol.

参考文献中间体

合成目标

【1】 Okano, K.; Asano, O.; Shimomura, N.; Kawahara, T.; Abe, S.; Miyazawa, S.; Miyamoto, M.; Yoshimura, H.; Harada, K.; Nagaoka, J.; Kawata, T.; Yoshimura, T.; Suzuki, H.; Souda, S.; Machida, Y.; Katayama, K.; Yamatsu, I. (Eisai Co., Ltd.); Glycerin deriv. and its pharmacological use. AU 8937213; EP 0353474; JP 1990131467; JP 1996231508; US 5037827; US 5273985; US 5476863; US 5476864 .
【2】 Okano, K.; Shimomura, N.; Asano, O.; et al.; Okano, K., Asano, O., Shimomura, N. et al. Structure-activity relationships of platelet activating factor (PAF) antagonists. 198th ACS Natl Meet (Sept 10-15, Miami Beach) 1989, Abst MEDI 55.
【3】 Prous, J.; Castaner, J.; E-5880. Drugs Fut 1992, 17, 12, 1082.

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)	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(III)	13581	2-methoxy-3-[(phenoxycarbonyl)oxy]propyl phenyl carbonate		C₁₈H₁₈O₇	详情	详情
(IV)	13582	2-Pyridinylmethanamine; 2-Pyridinylmethylamine; 2-(Aminomethyl)pyridine	3731-51-9	C₆H₈N₂	详情	详情
(V)	13583	(5-oxo-6-phenyl-1,4-dioxan-2-yl)methyl 2-pyridinylmethylcarbamate		C₁₈H₁₈N₂O₅	详情	详情
(VI)	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(VII)	13585	2-methoxy-3-([[(2-pyridinylmethyl)amino]carbonyl]oxy)propyl 4-hydroxy-1-piperidinecarboxylate		C₁₇H₂₅N₃O₆	详情	详情
(VIII)	13586	1-Isocyanatooctadecane; octadecyl isocyanate	112-96-9	C₁₉H₃₇NO	详情	详情
(IX)	13587	2-methoxy-3-([[(2-pyridinylmethyl)amino]carbonyl]oxy)propyl 4-[(phenoxycarbonyl)oxy]-1-piperidinecarboxylate		C₂₄H₂₉N₃O₈	详情	详情
(X)	13588	2-methoxy-3-([[(2-pyridinylmethyl)amino]carbonyl]oxy)propyl 4-[[(octadecylamino)carbonyl]oxy]-1-piperidinecarboxylate		C₃₆H₆₂N₄O₇	详情	详情
(XI)	13589	1-Aminooctadecane; Octadecylamine; 1-Octadecanamine	124-30-1	C₁₈H₃₉N	详情	详情
(XII)	13590	2-Methoxybenzoyl chloride; o-Anisoyl chloride; 2-Anisoyl chloride	21615-34-9	C₈H₇ClO₂	详情	详情
(XIII)	13591	2-methoxy-3-([[(2-methoxybenzoyl)(2-pyridinylmethyl)amino]carbonyl]oxy)propyl 4-[[(octadecylamino)carbonyl]oxy]-1-piperidinecarboxylate		C₄₄H₆₈N₄O₉	详情	详情

Extended Information