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【结 构 式】 
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【分子编号】65694 【品名】1-Adamantanemethanol; 1-(Hydroxymethyl)adamantane; 1-Tricyclo[3.3.1.1(3,7)]decanemethanol 【CA登记号】770-71-8 |
【 分 子 式 】C11H18O 【 分 子 量 】166.26332 【元素组成】C 79.46% H 10.91% O 9.62% |
合成路线1
该中间体在本合成路线中的序号：(XVII)The intermediate (S)-adamantylglycine (I) can be prepared as follows. Reduction of adamantane-1-carboxylic acid (XVI) using LiAlH4 in THF gives the primary alcohol (XVII), which is oxidized to aldehyde (XVIII) under Swern conditions. Adamantane-1-carbaldehyde (XVIII) is then condensed with (R)-phenylglycinol (XIX) and KCN in the presence of NaHSO3 to yield the chiral aminonitrile (XX). After acidic hydrolysis of nitrile (XX) to the corresponding amino acid (XXI), the chiral auxiliary group is removed by hydrogenolysis over Pearlman’s catalyst to furnish intermediate (I) (1, 6). Scheme 2.
| 【1】 Robl, J.A., Sulsky, R.B., Betebenner, D.A., Magnin, D.R., Hamann, L.G., Augeri, D.J. (Bristol-Myers Squibb Co.). Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method. EP 1261586, JP 2003531118, US 6395767, WO 0168603. |
| 【6】 Augeri, D.J., Robl, J.A., Betebenner, D.A. et al. Discovery and preclinical profile of saxagliptin (BMS-477118): A highly potent, long-acting, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem 2005, 48(15): 5025-37. |
| 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) | 65644 | C35H41INOPSSi | 详情 | 详情 | ||
| (XVI) | 65693 | 1-Adamantanecarboxylic acid; Adamantane-1-carboxylic acid; Tricyclo[3.3.1.1(3,7)]decan-1-Carboxylic acid | 828-51-3 | C11H16O2 | 详情 | 详情 |
| (XVII) | 65694 | 1-Adamantanemethanol; 1-(Hydroxymethyl)adamantane; 1-Tricyclo[3.3.1.1(3,7)]decanemethanol | 770-71-8 | C11H18O | 详情 | 详情 |
| (XVIII) | 65695 | 1-Adamantylcarboxaldehyde; Tricyclo[3.3.1.1(3,7)]decane-1-carboxaldehyde; 1-Formyladamantane | 2094-74-8 | C11H16O | 详情 | 详情 |
| (XIX) | 14376 | (2R)-2-amino-2-phenyl-1-ethanol; (R)-(-)-2-phenylglycinol; (R)-2-amino-2-phenyl-1-ethanol | 56613-80-0 | C8H11NO | 详情 | 详情 |
| (XX) | 65696 | (alphaS)-alpha-[[(1R)-2-Hydroxy-1-phenylethyl]amino]-tricyclo[3.3.1.1(3,7)]decane-1-acetonitrile | 361441-95-4 | C20H26N2O | 详情 | 详情 |
| (XXI) | 65697 | C20H27NO3 | 详情 | 详情 |