【结 构 式】 |
【分子编号】13588 【品名】2-methoxy-3-([[(2-pyridinylmethyl)amino]carbonyl]oxy)propyl 4-[[(octadecylamino)carbonyl]oxy]-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C36H62N4O7 【 分 子 量 】662.91104 【元素组成】C 65.23% H 9.43% N 8.45% O 16.89% |
合成路线1
该中间体在本合成路线中的序号:(X)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.
【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 |