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【结 构 式】 
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【分子编号】43543 【品名】(E,10R)-5-amino-10-[(benzylsulfonyl)amino]-3,11-dioxo-1-phenyl-2-oxa-4,6,12-triaza-4-tetradecen-14-oic acid 【CA登记号】 |
【 分 子 式 】C23H29N5O7S 【 分 子 量 】519.57876 【元素组成】C 53.17% H 5.63% N 13.48% O 21.56% S 6.17% |
合成路线1
该中间体在本合成路线中的序号：(XII)Solution-phase synthesis: Protection of the side-chain of Boc-Arg-OH (IX) by treatment with Cbz-Cl in aqueous NaHCO3 yields Boc-Arg(Cbz)-OH (X), which is then converted into arginine lactam (XI) by a first treatment with isobutyl chloroformate (i-BuO2CCl) and NMM in THF followed by Boc deprotection with HCl/dioxane. Condensation of N-deprotected lactam (XI) with protected dipeptide (XII) by means of BOP/DIEA in DMF provides the tripeptide lactam (XIII), which is finally reduced with LiAlH4 in THF and hydrogenated over Pd/C for protecting group removal.
| 【1】 Marlowe, C.K.; Sinha, U.; Scarborough, R.M.; Gunn, A.C.; Design, synthesis and structure-activity relationship of a series of arginine aldehyde factor Xa inhibitors. Part 1: Structures based on the (D)-Arg-Gly-Arg tripeptide sequence. Bioorg Med Chem Lett 2000, 10, 1, 13. |
| 【2】 Marlowe, C.K.; Scarborough, R.M.; Laibelman, A.M.; Sinha, U.; Zhu, B.-Y. (COR Therapeutics, Inc.); Inhibitors of factor Xa. EP 0846125; JP 1999507626; US 5919765; WO 9640743 . |
| 【3】 Marlowe, C.K.; Scarborough, R.M.; Laibelman, A.M.; Sinha, U.; Zhu, B.-Y. (COR Therapeutics, Inc.); Inhibitors of factor Xa. US 5721214 . |
| 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) | 14073 | (2S)-5-[[Amino(imino)methyl]amino]-2-[(tert-butoxycarbonyl)amino]pentanoic acid | 13726-76-6 | C11H22N4O4 | 详情 | 详情 |
| (X) | 14074 | (2S)-5-[(Amino[[(benzyloxy)carbonyl]imino]methyl)amino]-2-[(tert-butoxycarbonyl)amino]pentanoic acid | C19H28N4O6 | 详情 | 详情 | |
| (XI) | 43542 | benzyl (E)-amino[(3S)-3-amino-2-oxopiperidinyl]methylidenecarbamate | C14H18N4O3 | 详情 | 详情 | |
| (XII) | 43543 | (E,10R)-5-amino-10-[(benzylsulfonyl)amino]-3,11-dioxo-1-phenyl-2-oxa-4,6,12-triaza-4-tetradecen-14-oic acid | C23H29N5O7S | 详情 | 详情 | |
| (XIII) | 43544 | benzyl (E)-amino([(4R)-5-[(2-[[(3S)-1-(amino[[(benzyloxy)carbonyl]imino]methyl)-2-oxopiperidinyl]amino]-2-oxoethyl)amino]-4-[(benzylsulfonyl)amino]-5-oxopentyl]amino)methylidenecarbamate | C37H45N9O9S | 详情 | 详情 |