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【结 构 式】 
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【分子编号】28085 【品名】3-amino-2,2-dimethylpentanoic acid 【CA登记号】 |
【 分 子 式 】C7H15NO2 【 分 子 量 】145.20164 【元素组成】C 57.9% H 10.41% N 9.65% O 22.04% |
合成路线1
该中间体在本合成路线中的序号：(II)Metrifonate is totally unique among the acetylcholinesterase inhibitors currently used or proposed for the treatment of Alzheimer's disease because it is an inactive prodrug. The active compound dichlorvos, (2,2-dichlorovinyl dimethylphosphate; DDVP), is formed in a nonenzymatic reaction by hydrolysis and elimination of HCl followed by rearrangement of an intermediate according to Scheme.
| 【1】 Mucke, H.A.M.; Metrifonate. Drugs Fut 1998, 23, 5, 491. |
| 【2】 Giang, P.A.; Barthel, W.F.; Hall, S.A.; Dialkylalpha-hydroxyphosphonates derived from chloral. J Am Chem Soc 1954, 76, 4186-7. |
合成路线2
该中间体在本合成路线中的序号：(I)Protection of beta-alanine derivative (I) with di-tert-butyl dicarbonate afforded the tert-butyl carbamate (II). This was condensed with ethyl piperidine-4-acetate (III) using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyuronium hexafluorophosphate (HATU) and diisopropyl ethylamine to give amide (IV). Subsequent Boc deprotection of (IV) with trifluoroacetic acid provided amine (V), which was coupled with 2-fluoro-4-cyanobenzoic acid (VI) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and 1-hydroxybenzotriazole yielding (VII). Treatment of the resulting cyanobenzamide (VII) with SH2 and Et3N produced the corresponding thioamide, which was S-alkylated with MeI to give (VIII). Finally, displacement of the methylthio group of (VIII) with thiazolidine (IX) furnished the corresponding amidine.
| 【1】 Hayashi, Y.; Harada, T.; Katada, J.; et al.; GPIIb/IIIa integrin antagonists with the new conformational restriction unit, trisubstituted beta-amino acid derivatives, and substituted benzamidine structure. J Med Chem 1998, 41, 12, 2345. |
| 【2】 Hayashi, Y.; Harada, T.; Tachiki, A.; Katada, J. (Nippon Steel Corp.); Fibrinogen receptor antagonists and medicinal preparations containing the same as the active ingredient. EP 0852225; JP 1998017550; WO 9749682 . |
| 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) | 28085 | 3-amino-2,2-dimethylpentanoic acid | C7H15NO2 | 详情 | 详情 | |
| (II) | 28086 | 3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpentanoic acid | C12H23NO4 | 详情 | 详情 | |
| (III) | 28087 | 4-Piperidineacetic acid ethyl ester; ethyl 2-(4-piperidinyl)acetate | C9H17NO2 | 详情 | 详情 | |
| (IV) | 28088 | ethyl 2-(1-[3-[(tert-butoxycarbonyl)amino]-2,2-dimethylpentanoyl]-4-piperidinyl)acetate | C21H38N2O5 | 详情 | 详情 | |
| (V) | 28089 | ethyl 2-[1-(3-amino-2,2-dimethylpentanoyl)-4-piperidinyl]acetate | C16H30N2O3 | 详情 | 详情 | |
| (VI) | 28090 | 4-cyano-2-fluorobenzoic acid | C8H4FNO2 | 详情 | 详情 | |
| (VII) | 28091 | ethyl 2-(1-[3-[(4-cyano-2-fluorobenzoyl)amino]-2,2-dimethylpentanoyl]-4-piperidinyl)acetate | C24H32FN3O4 | 详情 | 详情 | |
| (VIII) | 28092 | ethyl 2-[1-[3-([2-fluoro-4-[imino(methylsulfanyl)methyl]benzoyl]amino)-2,2-dimethylpentanoyl]-4-piperidinyl]acetate | C25H36FN3O4S | 详情 | 详情 | |
| (IX) | 28093 | 1,3-thiazolidine | 504-78-9 | C3H7NS | 详情 | 详情 |