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【结 构 式】 
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【分子编号】52244 【品名】methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate 【CA登记号】 |
【 分 子 式 】C28H35NO5S 【 分 子 量 】497.65564 【元素组成】C 67.58% H 7.09% N 2.81% O 16.07% S 6.44% |
合成路线1
该中间体在本合成路线中的序号：(V)5-Hydroxybenzothiophene-3-carboxylic acid (I) was esterified with acetic anhydride in pyridine to afford the 5-acetoxy derivative (II). Treatment of (II) with thionyl chloride produced acid chloride (III), which was condensed with the previously reported bicyclic amine (IV), yielding amide (V). The ester groups of (V) were finally hydrolyzed under basic conditions to furnish the target compound.
| 【1】 Tsuri, T.; Honma, T.; Hiramatsu, Y.; Okada, T.; Hashizume, H.; Mitsumori, S.; Inagaki, M.; Arimura, A.; Yasui, K.; Asanuma, F.; Kishino, J.; Ohtani, M.; Bicyclo[2.2.1]heptane and 6,6-dimethylbicyclo[3.1.1]heptane derivatives: Orally active, potent, and selective prostaglandin D2 receptor antagonists. J Med Chem 1997, 40, 22, 3504. |
| 【2】 Arimura, A.; Honma, T.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Benzothiophenecarboxamide derivs. and PGD2 antagonists comprising them. EP 0944614; JP 2000514824; US 6083974; WO 9825919 . |
| 【3】 Arimura, A. (Shionogi & Co. Ltd.); Remedies for itching containing PGD2 antagonists. EP 1084711; WO 9962555 . |
| 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) | 52240 | 5-hydroxy-1-benzothiophene-3-carboxylic acid | C9H6O3S | 详情 | 详情 | |
| (II) | 52241 | 5-(acetyloxy)-1-benzothiophene-3-carboxylic acid | C11H8O4S | 详情 | 详情 | |
| (III) | 52242 | 3-(chlorocarbonyl)-1-benzothiophen-5-yl acetate | C11H7ClO3S | 详情 | 详情 | |
| (IV) | 52243 | methyl (Z)-7-[(1R,2R,3S,5R)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate | C17H29NO2 | 详情 | 详情 | |
| (V) | 52244 | methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate | C28H35NO5S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XLVII)Coupling of amino ester (XLIV) with carboxylic acid (IX) by means of EDC and HOBt produced the corresponding amide ester (XLV). In a related procedure, the analogous amino methyl ester (XLVI) was coupled with acid chloride (XV) to yield amide (XLVII). The title compound was then obtained by hydrolysis of the ethyl ester (XLV) with LiOH or by NaOH hydrolysis of diester (XLVII).
| 【1】 Tsuri, T.; Honma, T.; Hiramatsu, Y.; Okada, T.; Hashizume, H.; Mitsumori, S.; Inagaki, M.; Arimura, A.; Yasui, K.; Asanuma, F.; Kishino, J.; Ohtani, M.; Bicyclo[2.2.1]heptane and 6,6-dimethylbicyclo[3.1.1]heptane derivatives: Orally active, potent, and selective prostaglandin D2 receptor antagonists. J Med Chem 1997, 40, 22, 3504. |
| 【2】 Arimura, A.; Honma, T.; Hiramatsu, Y. (Shionogi & Co. Ltd.); Benzothiophenecarboxamide derivs. and PGD2 antagonists comprising them. EP 0944614; JP 2000514824; US 6083974; WO 9825919 . |
| 【3】 Cai, D.; Larsen, R.; Journet, M.; Campos, K. (Merck & Co., Inc.); Process for the preparation of PGD2 antagonist. WO 0232892 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 52240 | 5-hydroxy-1-benzothiophene-3-carboxylic acid | C9H6O3S | 详情 | 详情 | |
| (XV) | 52242 | 3-(chlorocarbonyl)-1-benzothiophen-5-yl acetate | C11H7ClO3S | 详情 | 详情 | |
| (XLIV) | 60688 | ethyl (Z)-7-[(1R,2R,3S,5R)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate | C18H31NO2 | 详情 | 详情 | |
| (XLV) | 60689 | ethyl (Z)-7-((1R,2R,3S,5R)-2-{[(5-hydroxy-1-benzothiophen-3-yl)carbonyl]amino}-6,6-dimethylbicyclo[3.1.1]hept-3-yl)-5-heptenoate | C27H35NO4S | 详情 | 详情 | |
| (XLVI) | 52243 | methyl (Z)-7-[(1R,2R,3S,5R)-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate | C17H29NO2 | 详情 | 详情 | |
| (XLVII) | 52244 | methyl 7-[2-({[5-(acetyloxy)-1-benzothiophen-3-yl]carbonyl}amino)-6,6-dimethylbicyclo[3.1.1]hept-3-yl]-5-heptenoate | C28H35NO5S | 详情 | 详情 |