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【结 构 式】 
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【分子编号】43463 【品名】(2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propionic acid 【CA登记号】 |
【 分 子 式 】C18H16N2O4S 【 分 子 量 】356.40212 【元素组成】C 60.66% H 4.52% N 7.86% O 17.96% S 9% |
合成路线1
该中间体在本合成路线中的序号：(XII)Amine intermediate (XIV) has been obtained as follows: N-(Carbobenzoxy)-L-aspartic acid alpha-benzyl ester (VII) was converted to acid chloride (VIII) and then coupled to 2-aminophenyl disulfide (IX) to afford the bis-amide (X). Reductive cleavage of the disulfide group of (X), followed by basic cyclization, produced the benzothiazole (XI) (2). Hydrolysis of the benzyl ester group of (XI) and subsequent coupling of the resulting carboxylic acid (XII) with piperidine (VI) gave amide (XIII). The carbobenzoxy group of (XII) was then cleaved with HBr in HOAc, yielding intermediate amine (XIV).
| 【1】 Baettig, U.; et al.; The design and synthesis of thrombin inhibitors: Analogues of MD805 containing non-polar surrogates for arginine at the P1 position. Bioorg Med Chem Lett 2000, 10, 14, 1563. |
| 【2】 Smith, G.P.; Brundish, D.E.; Menear, K.A.; Walker, C.V.; Herold, P.; Fullerton, J.D.; Allen, M.C.; Le Grand, D.M.; Kane, P.D.; Cockcroft, X.-L.; Wathey, W.B.; Butler, P.I.; Hatto, J.D.I.; Hayler, J.D. (Novartis AG); Tetrahydroquinoline inhibitors of trypsin and thrombin. GB 2312674 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 28517 | 4-(2-fluoroethyl)piperidine | C7H14FN | 详情 | 详情 | |
| (VII) | 43458 | (3S)-4-(benzyloxy)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutyric acid | 4779-31-1 | C19H19NO6 | 详情 | 详情 |
| (VIII) | 43459 | benzyl (2S)-2-[[(benzyloxy)carbonyl]amino]-4-chloro-4-oxobutanoate | C19H18ClNO5 | 详情 | 详情 | |
| (IX) | 43460 | 2-[(2-aminophenyl)disulfanyl]aniline; 2-[(2-aminophenyl)disulfanyl]phenylamine | 1141-88-4 | C12H12N2S2 | 详情 | 详情 |
| (X) | 43461 | benzyl (2S)-4-[2-([2-[((3S)-4-(benzyloxy)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutanoyl)amino]phenyl]disulfanyl)anilino]-2-[[(benzyloxy)carbonyl]amino]-4-oxobutanoate | C50H46N4O10S2 | 详情 | 详情 | |
| (XI) | 43462 | benzyl (2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propanoate | C25H22N2O4S | 详情 | 详情 | |
| (XII) | 43463 | (2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propionic acid | C18H16N2O4S | 详情 | 详情 | |
| (XIII) | 43464 | benzyl (1S)-1-(1,3-benzothiazol-2-ylmethyl)-2-[4-(2-fluoroethyl)-1-piperidinyl]-2-oxoethylcarbamate | C25H28FN3O3S | 详情 | 详情 | |
| (XIV) | 43465 | (2S)-2-amino-3-(1,3-benzothiazol-2-yl)-1-[4-(2-fluoroethyl)-1-piperidinyl]-1-propanone | C17H22FN3OS | 详情 | 详情 |