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【结 构 式】 
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【药物名称】 【化学名称】(-)-(4aR,10bR)-1-(4-Hydroxybenzoyl)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile 【CA登记号】 【 分 子 式 】C21H20N2O4 【 分 子 量 】364.40455 |
【开发单位】National Taiwan University (Originator) 【药理作用】RENAL-UROLOGIC DRUGS, Urinary Incontinence Therapy, Potassium Channel Activators |
合成路线1
Ring opening of the chiral epoxide (I) with 2-aminoethanol gave the trans-aminoalcohol (II). Subsequent intramolecular cyclization of (II) under Mitsunobu conditions afforded the chromenooxazine tricyclic system (III). The NH group of (III) was then acylated with anisoyl chloride (IV), yielding amide (V). This compound underwent epimerization at the C-10b position upon treatment with NaH to produce the more stable cis-fused isomer (VI). The methyl ether group of (VI) was finally cleaved by treatment with boron tribromide to furnish the corresponding phenol.
| 【1】 Lin, Y.-C.; Tsai, M.-C.; Chiu, H.-I.; Yu, H.-C.; Cheng, C.-Y.; N-acyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano-[3,4-b][1,4]oxazine-9-carbonitriles as bladder-selective potassium channel openers. Bioorg Med Chem 2001, 9, 2, 383. |
| 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) | 48196 | (1aR,7bR)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromene-6-carbonitrile | C12H11NO2 | 详情 | 详情 | |
| (II) | 48192 | (3R,4S)-3-hydroxy-4-[(2-hydroxyethyl)amino]-2,2-dimethyl-3,4-dihydro-2H-chromene-6-carbonitrile | C14H18N2O3 | 详情 | 详情 | |
| (III) | 48193 | (4aR,10bS)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b][1,4]oxazine-9-carbonitrile | C14H16N2O2 | 详情 | 详情 | |
| (IV) | 22671 | 4-Methoxybenzoyl chloride; p-Methoxybenzoyl chloride; 4-Anisoyl chloride | 100-07-2 | C8H7ClO2 | 详情 | 详情 |
| (V) | 48194 | (4aR,10bS)-1-(4-methoxybenzoyl)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b][1,4]oxazine-9-carbonitrile | C22H22N2O4 | 详情 | 详情 | |
| (VI) | 48195 | (4aR,10bR)-1-(4-methoxybenzoyl)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydrochromeno[3,4-b][1,4]oxazine-9-carbonitrile | C22H22N2O4 | 详情 | 详情 |