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【结 构 式】 
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【分子编号】26056 【品名】3-(aminomethyl)-5-methylhexanoic acid 【CA登记号】130912-52-6 |
【 分 子 式 】C8H17NO2 【 分 子 量 】159.22852 【元素组成】C 60.35% H 10.76% N 8.8% O 20.1% |
与该中间体有关的原料药合成路线共 3 条
合成路线1
该中间体在本合成路线中的序号：(XXIII)3) The reaction of diethyl malonate (XVIII) with 3-methylbutanal (XIX) by means of dipropylamine in acetic acid gives the corresponding 2-(3-methylbutylidene)malonate derivative (XX), which is treated with KCN to yield the corresponding addition compound (XXI). The decarboxylative hydrolysis of (XXI) with KOH affords 3-cyano-5-methylhexanoic acid (XXII), which is reduced with H2 over Ni to yield racemic pregabalin (XXIII). Finally, this racemate is submitted to optical resolution with (S)-(+)-mandelic acid.
| 【1】 Bryans, J.S.; Wustrow, D.J.; 3-Substituted GABA analogs with central nervous system activity: A review. Med Res Rev 1999, 19, 2, 149. |
| 【2】 Newhouse, B.J.; Ibrahim, P.; Burgess, L.E.; et al.; Potent selective nonpeptidic inhibitors of human lung tryptase. Proc Natl Acad Sci USA 1999, 96, 15, 8348. |
| 【3】 Mulhern, T.; Sobieray, D.M.; Huckabee, B.K.; Grote, T.M.; Titus, R.D. (Pfizer Inc.); Method of making (S)-3-(aminomethyl)-5-methylhexanoic acid. WO 9640617 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (XIX) | 26052 | 3-methylbutanal | 590-86-3 | C5H10O | 详情 | 详情 |
| (XX) | 26053 | diethyl 2-(3-methylbutylidene)malonate | C12H20O4 | 详情 | 详情 | |
| (XXI) | 26054 | diethyl 2-(1-cyano-3-methylbutyl)malonate | C13H21NO4 | 详情 | 详情 | |
| (XXII) | 26055 | 3-cyano-5-methylhexanoic acid | C8H13NO2 | 详情 | 详情 | |
| (XXIII) | 26056 | 3-(aminomethyl)-5-methylhexanoic acid | 130912-52-6 | C8H17NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)
| 【1】 Zhang GS, Yang XP, Ma, YQ, et aL. 2006. Method for preparation of Pregabalin and its intermediate. W0 2006136087．(本专利属于Nhwa Pharma Corporation, Peop Rep China) |
| 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) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (II) | 26052 | 3-methylbutanal | 590-86-3 | C5H10O | 详情 | 详情 |
| (III) | 66601 | diethyl 3-isobutylpentanedioate | C13H24O4 | 详情 | 详情 | |
| (IV) | 26065 | 3-isobutylpentanedioic acid | C9H16O4 | 详情 | 详情 | |
| (V) | 66602 | 4-isobutylpiperidine-2,6-dione | C9H15NO2 | 详情 | 详情 | |
| (VI) | 26056 | 3-(aminomethyl)-5-methylhexanoic acid | 130912-52-6 | C8H17NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)
| 【1】 Chen A, Zhang JJ. 2005. Synthesis of Pregabalin. 中国医药工业杂志，35: 195～196 |
| 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) | 26065 | 3-isobutylpentanedioic acid | C9H16O4 | 详情 | 详情 | |
| (II) | 26066 | 4-isobutyldihydro-2H-pyran-2,6(3H)-dione | C9H14O3 | 详情 | 详情 | |
| (III) | 66612 | 3-(2-(aminooxy)-2-oxoethyl)-5-methylhexanoic acid | C9H17NO4 | 详情 | 详情 | |
| (IV) | 26056 | 3-(aminomethyl)-5-methylhexanoic acid | 130912-52-6 | C8H17NO2 | 详情 | 详情 |
Extended Information