|
【结 构 式】 
|
【分子编号】20989 【品名】Diethylazadicarboxylate; Diethyl Azodiformate; Azodiformic Acid Diethyl Ester; Diethyl Azodicarboxylate; Azodicarboxylic Acid Diethyl Ester; Diethyl 1,2-diazenedicarboxylate 【CA登记号】1972-28-7 |
【 分 子 式 】C6H10N2O4 【 分 子 量 】174.15648 【元素组成】C 41.38% H 5.79% N 16.09% O 36.75% |
合成路线1
该中间体在本合成路线中的序号：(XIX)The protection of (XVI) with dihydropyran as usual gives the fully protected compound (XVII), which is deacetylated with K2CO3 in methanol to the 9alpha-hydroxy derivative (XVIII). The formylation of (XVIII) with diethyl azodiformate (XIX) and triphenylphosphine - formic acid in THF gives the 9beta-formyloxy compound (XX), which is hydrolyzed with K2CO3 as before to the 9beta-hydroxy compound (XXI). The tosylation of (XXI) with tosyl chloride in pyridine yields the tosylate (XXII), which is deprotected with p-toluenesulfonic acid affording the 9beta-tosyloxy-11alpha,15alpha-dihydroxyprostaglandin (XXIII). Finally, this compound is cyclized with sodium azide in hot DMSO.
| 【1】 Masuda, Y. (Ono Pharmaceutical Co., Ltd.); New method of treatment using prostaglandin analogues. EP 0169725; JP 1986030519 . |
| 【2】 Prous, J.; Castaner, J.; OP-2507. Drugs Fut 1989, 14, 6, 525. |
| 【3】 Iguchi, S.; et al.; T. Synthesis of 15-cis-(4-n-propylcyclohexyl)-16,17,18,19, 20-pentanor-9-deoxy-6,9-alpha-nitriloprostaglandin F2 methyl ester (OP-2507), a novel anti-cerebral ischemic agent. Chem Pharm Bull 1988, 36, 3, 1128. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI) | 20985 | methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3S)-3-hydroxy-3-(4-propylcyclohexyl)-1-propenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C33H54O7 | 详情 | 详情 | |
| (XVII) | 20987 | methyl (Z)-7-[(1R,2S,3R,5S)-5-(acetoxy)-2-[(E,3S)-3-(4-propylcyclohexyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C39H64O8 | 详情 | 详情 | |
| (XVIII) | 20988 | methyl (Z)-7-[(1R,2S,3R,5S)-5-hydroxy-2-[(E,3S)-3-(4-propylcyclohexyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C37H62O7 | 详情 | 详情 | |
| (XIX) | 20989 | Diethylazadicarboxylate; Diethyl Azodiformate; Azodiformic Acid Diethyl Ester; Diethyl Azodicarboxylate; Azodicarboxylic Acid Diethyl Ester; Diethyl 1,2-diazenedicarboxylate | 1972-28-7 | C6H10N2O4 | 详情 | 详情 |
| (XX) | 20990 | methyl (Z)-7-[(1R,2S,3R,5R)-5-(formyloxy)-2-[(E,3S)-3-(4-propylcyclohexyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C38H62O8 | 详情 | 详情 | |
| (XXI) | 20991 | methyl (Z)-7-[(1R,2S,3R,5R)-5-hydroxy-2-[(E,3S)-3-(4-propylcyclohexyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C37H62O7 | 详情 | 详情 | |
| (XXII) | 20992 | methyl (Z)-7-[(1R,2S,3R,5R)-5-[[(4-methylphenyl)sulfonyl]oxy]-2-[(E,3S)-3-(4-propylcyclohexyl)-4-(tetrahydro-2H-pyran-2-yloxy)-1-butenyl]-3-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclopentyl]-5-heptenoate | C44H68O9S | 详情 | 详情 | |
| (XXIII) | 20993 | methyl (Z)-7-((1R,2R,3R,5R)-3-hydroxy-2-[(E,3S)-3-hydroxy-3-(4-propylcyclohexyl)-1-propenyl]-5-[[(4-methylphenyl)sulfonyl]oxy]cyclopentyl)-5-heptenoate | C32H48O7S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)A short and efficient synthesis of xemilofiban has been achieved as follows: The reaction of ethyl chloroformate (I) with trimethylsilylacetylene (II) by means of butyllithium gives ethyl 3-(trimethylsilyl)propyonate (III), which is condensed with the lithium salt of ethyl acetate (IV) yielding ethyl 5-(trimethylsilyl)-3-oxo-4-pentynoate (V). The selective reduction of (V) with lyophilized baker's yeast (Saccharomyces cerevisiae, Sigma type II) affords ethyl 3(R)-hydroxy-5-(trimethylsilyl)-4-pentynoate (VI), which by reaction with ammonia (VII), diethyl azodicarboxylate (VIII) and triphenylphosphine, followed by hydrolysis with water gives 3(S)-amino-5-(trimethylsilyl)-4-pentynoate (IX). Finally, this compound is condensed with N-(4-amidinophenyl)succinamic acid (XI) by means of isobutyl chloroformate and N-methylmorpholine (NMM). The intermediate succinamic acid (XI) has been obtained by condensation of 4-aminobenzamidine (XII) with succinic anhydride (XIII) in DMF.
| 【1】 Cossy, J.; Schmitt, A.; Cinquin, C.; Buisson, D.; Belotti, D.; A very short, efficient and inexpensive synthesis of the prodrug form of SC-54701A a platelet aggregation inhibitor. Bioorg Med Chem Lett 1997, 7, 13, 1699. |
| 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) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
| (II) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (III) | 23898 | ethyl 3-(trimethylsilyl)-2-propynoate | 29394-58-9 | C8H14O2Si | 详情 | 详情 |
| (IV) | 23899 | lithium 1-ethoxy-1-ethylenolate | C4H7LiO2 | 详情 | 详情 | |
| (V) | 23900 | ethyl 3-oxo-5-(trimethylsilyl)-4-pentynoate | C10H16O3Si | 详情 | 详情 | |
| (VI) | 23901 | ethyl (3R)-3-hydroxy-5-(trimethylsilyl)-4-pentynoate | C10H18O3Si | 详情 | 详情 | |
| (VIII) | 20989 | Diethylazadicarboxylate; Diethyl Azodiformate; Azodiformic Acid Diethyl Ester; Diethyl Azodicarboxylate; Azodicarboxylic Acid Diethyl Ester; Diethyl 1,2-diazenedicarboxylate | 1972-28-7 | C6H10N2O4 | 详情 | 详情 |
| (IX) | 23904 | ethyl (3S)-3-amino-5-(trimethylsilyl)-4-pentynoate | C10H19NO2Si | 详情 | 详情 | |
| (X) | 16297 | ethyl (3S)-3-amino-4-pentynoate | C7H11NO2 | 详情 | 详情 | |
| (XI) | 16296 | 4-[4-[amino(imino)methyl]anilino]-4-oxobutyric acid | C11H13N3O3 | 详情 | 详情 | |
| (XII) | 16295 | 4-aminobenzenecarboximidamide hydrochloride; 4-aminobenzamidine | 3858-83-1 | C7H9N3 | 详情 | 详情 |
| (XIII) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |