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【结 构 式】 
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【分子编号】38306 【品名】ethyl 3-[((3S)-3-[[(7-chlorothieno[2,3-c]pyridin-2-yl)sulfonyl]amino]-2-oxopyrrolidinyl)methyl]-4-hydroxybenzenecarboximidoate 【CA登记号】 |
【 分 子 式 】C21H21ClN4O5S2 【 分 子 量 】509.0064 【元素组成】C 49.55% H 4.16% Cl 6.97% N 11.01% O 15.72% S 12.6% |
合成路线1
该中间体在本合成路线中的序号：(XIX)Thienylacrylic acid (XII), prepared from thiophene aldehyde (XI), was activated as the mixed anhydride with ethyl chloroformate and then treated with NaN3 to yield acyl azide (XIII). Cyclization of (XIII) in the presence of Bu3P in boiling diphenyl ether generated the thienopyridine system (XIV). Chlorination of (XIV) with POCl3 afforded the chloro derivative (XV). After lithium-bromine exchange with n-butyllithium, the resulting organolithium derivative (XVI) was treated with SO2 and further oxidized to sulfonyl chloride (XVII) with SO2Cl2. Coupling of (XVII) with aminopyrrolidinone (X) yielded sulfonamide (XVIII). Conversion of the nitrile of (XVIII) to the corresponding imidate (XIX), followed by reaction with ammonia produced benzamidine (XX). Finally, hydrogenolytic dechlorination of (XX) over Pd/C provided the title compound.
| 【1】 Ewing, W.R.; Davis, R.S.; Becker, M.R.; et al.; Synthesis, SAR and in vivo activity of novel thienopyridine sulfonamide pyrrolidinones as factor Xa inhibitors. Bioorg Med Chem Lett 1999, 9, 18, 2753. |
| 【2】 Ewing, W.R.; Becker, M.R.; Choi-Sledeski, Y.M.; Pauls, H.W.; McGarry, D.G.; Davis, R.S.; Spada, A.P. (Aventis Pharma SA); Substd. sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclamide cpds.. EP 0894088; JP 2000505815; US 5731315; WO 9824784 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 31677 | 3-[[(3S)-3-amino-2-oxopyrrolidinyl]methyl]-4-hydroxybenzonitrile | C12H13N3O2 | 详情 | 详情 | |
| (XI) | 31660 | 5-bromo-3-thiophenecarbaldehyde | C5H3BrOS | 详情 | 详情 | |
| (XII) | 38299 | (E)-3-(5-bromo-3-thienyl)-2-propenoic acid | C7H5BrO2S | 详情 | 详情 | |
| (XIII) | 38300 | (E)-3-(5-bromo-3-thienyl)-2-propenoyl azide | C7H4BrN3OS | 详情 | 详情 | |
| (XIV) | 38301 | 2-bromothieno[2,3-c]pyridin-7(6H)-one | C7H4BrNOS | 详情 | 详情 | |
| (XV) | 38302 | 2-bromo-7-chlorothieno[2,3-c]pyridine | C7H3BrClNS | 详情 | 详情 | |
| (XVI) | 38303 | (7-chlorothieno[2,3-c]pyridin-2-yl)lithium | C7H3ClLiNS | 详情 | 详情 | |
| (XVII) | 38304 | 7-chlorothieno[2,3-c]pyridine-2-sulfonyl chloride | C7H3Cl2NO2S2 | 详情 | 详情 | |
| (XVIII) | 38305 | 7-chloro-N-[(3S)-1-(5-cyano-2-hydroxybenzyl)-2-oxopyrrolidinyl]thieno[2,3-c]pyridine-2-sulfonamide | C19H15ClN4O4S2 | 详情 | 详情 | |
| (XIX) | 38306 | ethyl 3-[((3S)-3-[[(7-chlorothieno[2,3-c]pyridin-2-yl)sulfonyl]amino]-2-oxopyrrolidinyl)methyl]-4-hydroxybenzenecarboximidoate | C21H21ClN4O5S2 | 详情 | 详情 | |
| (XX) | 38307 | 3-[((3S)-3-[[(7-chlorothieno[2,3-c]pyridin-2-yl)sulfonyl]amino]-2-oxopyrrolidinyl)methyl]-4-hydroxybenzenecarboximidamide | C19H18ClN5O4S2 | 详情 | 详情 |