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【结 构 式】 
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【分子编号】31422 【品名】(2S)-3-amino-2-[(phenylsulfonyl)amino]propionic acid 【CA登记号】 |
【 分 子 式 】C9H12N2O4S 【 分 子 量 】244.27136 【元素组成】C 44.25% H 4.95% N 11.47% O 26.2% S 13.13% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Subsequent Mitsunobu condensation of (XIV) with N-trityl-L-serine methyl ester (XV) in the presence of DEAD and PPh3 produced the serine ether (XVI). Deprotection of the trityl group of (XVI) by means of trifluoroacetic acid and triethylsilane, followed by transfer hydrogenolysis of the benzyl ether with ammonium formate and Pd/C provided the deprotected intermediate (XVII). Finally, reduction of the ester group of (XVII) with LiAlH4 yielded the title compound.
| 【1】 Antithrombotic diamines. EP 0863755; US 6025382; WO 9725033 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 31419 | 4-[6-(benzyloxy)-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]-1-benzothiophen-2-yl]phenol | C34H33NO3S | 详情 | 详情 | |
| (XV) | 31420 | methyl (2S)-3-hydroxy-2-(tritylamino)propanoate | C23H23NO3 | 详情 | 详情 | |
| (XVI) | 31421 | methyl (2S)-3-(4-[6-(benzyloxy)-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]-1-benzothiophen-2-yl]phenoxy)-2-(tritylamino)propanoate | C57H54N2O5S | 详情 | 详情 | |
| (XVII) | 31422 | (2S)-3-amino-2-[(phenylsulfonyl)amino]propionic acid | C9H12N2O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The condensation of L-asparagine (I) with benzenesulfonyl chloride (II) in the presence of NaOH gave sulfonamide (III). Subsequent Hofmann rearrangement of (III) employing sodium hypobromite produced the diaminopropionic acid derivative (IV), which was protected as the tert-butyl ester (V) using isobutylene in the presence of H2SO4. Condensation of methyl 4-aminobenzoate (VI) with bis(2-chloroethyl)amine (VII) in refluxing butanol yielded the arylpiperazine (VIII), which was protected with di tert-butyl dicarbonate to give the corresponding carbamate (IX). Basic hydrolysis of the methyl ester of (IX) provided carboxylic acid (X). This was then coupled with amine (V) using benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) to afford amide (XI). Finally, deprotection of the tert-butyl ester and BOC group of (XI) with trifluoroacetic acid furnished the title compound.
| 【1】 Egbertson, M.S.; Turchi, L.M.; Hartman, G.D.; Halczenko, W.; Whitman, D.B.; Perkins, J.J.; Krause, A.E.; Ihle, N.; Claremon, D.A.; Hoffman, W.; Duggan, M.E. (Merck & Co., Inc.); Fibrinogen receptor antagonists. EP 0673247; JP 1996504194; WO 9412181 . |
| 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) | 25972 | S-(+)-Asparagine; S-(+)-2-Aminosuccinamic acid; L-Asparagine | 70-47-3 | C4H8N2O3 | 详情 | 详情 |
| (II) | 14713 | benzenesulfonyl chloride | 98-09-9 | C6H5ClO2S | 详情 | 详情 |
| (III) | 25973 | (2S)-4-amino-4-oxo-2-[(phenylsulfonyl)amino]butyric acid | C10H12N2O5S | 详情 | 详情 | |
| (IV) | 31422 | (2S)-3-amino-2-[(phenylsulfonyl)amino]propionic acid | C9H12N2O4S | 详情 | 详情 | |
| (V) | 31423 | tert-butyl (2S)-3-amino-2-[(phenylsulfonyl)amino]propanoate | C13H20N2O4S | 详情 | 详情 | |
| (VI) | 20537 | methyl 4-aminobenzoate | 619-45-4 | C8H9NO2 | 详情 | 详情 |
| (VII) | 21583 | 2-chloro-N-(2-chloroethyl)-1-ethanamine; Bis(2-chloroethyl)amine; 1,1'-iminobis(2-chloroethane); N,N-bis(2-chloroethyl)amine | 821-48-7 | C4H9Cl2N | 详情 | 详情 |
| (VIII) | 31424 | methyl 4-(1-piperazinyl)benzoate | C12H16N2O2 | 详情 | 详情 | |
| (IX) | 31425 | tert-butyl 4-[4-(methoxycarbonyl)phenyl]-1-piperazinecarboxylate | C17H24N2O4 | 详情 | 详情 | |
| (X) | 31426 | 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]benzoic acid | C16H22N2O4 | 详情 | 详情 | |
| (XI) | 31427 | tert-butyl 4-[4-[([(2S)-3-(tert-butoxy)-3-oxo-2-[(phenylsulfonyl)amino]propyl]oxy)carbonyl]phenyl]-1-piperazinecarboxylate | C29H39N3O8S | 详情 | 详情 |