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【结 构 式】 
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【药物名称】SMP-114 【化学名称】N2-[3-[1(S)-(2-Fluorobiphenyl-4-yl)ethyl]-5-isoxazolyl]-4-morpholinecarboxamidine hydrochloride 【CA登记号】 【 分 子 式 】C22H24ClFN4O2 【 分 子 量 】430.91358 |
【开发单位】Sumitomo Pharmaceuticals (Originator) 【药理作用】Antiarthritic Drugs, Disease-Modifying Drugs, Rheumatoid Arthritis, Treatment of, TREATMENT OF MUSCULOSKELETAL & CONNECTIVE TISSUE DISEASES |
合成路线1
The condensation of 2(S)-(2-fluorobiphenyl-4-yl)propionic acid (I) with tert-butyl cyanacetate (II) by means of lithium amide in THF gives lithium enolate (III), which is cyclized with hydroxylamine in aqueous DMF to yield the 5-aminoisoxazole (IV). Finally, this compound is condensed with morpholine-4-carbonitrile by means of lithium amide in toluene/tert-butanol to afford the target amidine.
| 【1】 Nakatsuka, M.; et al.; Novel disease modifying anti-rheumatic agents (DMARDs): Syntheses and SAR of 5-guanidinoisoxazoles. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 269. |
| 【2】 Ueno, Y.; Okada, S.; Nakatsuka, M.; Nishikaku, F. (Sumitomo Pharmaceuticals Co., Ltd.); Isoxazole derivs.. EP 0979226; JP 1999240873; US 6100260; WO 9847880 . |
| 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) | 52007 | (2S)-2-(2-fluoro[1,1'-biphenyl]-4-yl)propionic acid | C15H13FO2 | 详情 | 详情 | |
| (II) | 14330 | tert-Butyl cyanoacetate; tert-butyl 2-cyanoacetate | 1116-98-9 | C7H11NO2 | 详情 | 详情 |
| (III) | 52008 | C22H21FLiNO3 | 详情 | 详情 | ||
| (IV) | 52009 | 3-[(1S)-1-(2-fluoro[1,1'-biphenyl]-4-yl)ethyl]-5-isoxazolamine; 3-[(1S)-1-(2-fluoro[1,1'-biphenyl]-4-yl)ethyl]-5-isoxazolylamine | C17H15FN2O | 详情 | 详情 | |
| (V) | 52010 | 4-Morpholinecarbonitrile; Morpholine-4-carbonitrile; N-Cyanomorpholine | 1530-89-8 | C5H8N2O | 详情 | 详情 |