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【结 构 式】 
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【分子编号】33927 【品名】(1S,5R,13R,17S)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one 【CA登记号】 |
【 分 子 式 】C16H17NO4 【 分 子 量 】287.31532 【元素组成】C 66.89% H 5.96% N 4.88% O 22.27% |
合成路线1
该中间体在本合成路线中的序号：(I)Compound can be prepared in three different ways all starting from 14-hydroxydihydronormorphinone (I): 1) The condensation of (I) with cyclobutanecarboxyl chloride (A) by means of triethylamine in CH2Cl2 gives the bis(cyclobutylcarbonyl) derivative (II), which is then reduced and hydrolyzed with LiAlH4 in THF. 2) The condensation of (I) with cyclobutylmethyl bromide (B) in DMF gives the N-cyclobutylmethyl derivative (III), which is then reduced with NaBH4 in ethanol. 3) The reduction of (I) with NaBH4 as before gives 14-hydroxydihydronormophine (IV), which is then alkylated with cyclobutylmethyl bromide (B) in DMF.
| 【1】 Blumberg, H.; et al.; Verfahren zur Herstellung von N-substituierten 14-Hydroxydihydronormorphinen. CH 493522; DE 1670616; DE 1795707; ES 334942; FR 6112M; GB 1119270 . |
| 【2】 Blumberg, H.; et al.; 14-Hydroxydihydronormorphinone derivatives. US 3332950 . |
| 【3】 Castaner, J.; Roberts, P.J.; Nalbuphine. Drugs Fut 1977, 2, 9, 613. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 18589 | cyclobutanecarbonyl chloride | 5006-22-4 | C5H7ClO | 详情 | 详情 |
| (B) | 33931 | 1-(bromomethyl)cyclobutane;bromomethylcyclobutane;(Bromomethyl)cyclobutane;Cyclobutylmethyl bromide | 17247-58-4 | C5H9Br | 详情 | 详情 |
| (I) | 33927 | (1S,5R,13R,17S)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C16H17NO4 | 详情 | 详情 | |
| (II) | 33928 | (1S,5R,13R,17S)-4-(cyclobutylcarbonyl)-17-hydroxy-14-oxo-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-10-yl cyclobutanecarboxylate | C26H29NO6 | 详情 | 详情 | |
| (III) | 33929 | (1S,5R,13R,17S)-4-(cyclobutylmethyl)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C21H25NO4 | 详情 | 详情 | |
| (IV) | 33930 | (1S,5R,13R,14S,17S)-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-triene-10,14,17-triol | C16H19NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Noroxymorphindole (III) was prepared by Fischer indole synthesis from noroxymorphone (I) and phenylhydrazine (II) under acidic conditions. Alkylation of (III) with 2-methyl-2-propenyl bromide (IV) in the presence of NaHCO3 in DMF afforded the title compound.
| 【1】 McLamore, S.; et al.; Effect of N-alkyl and N-alkenyl substituents in noroxymorphindole, 17-substituted-6,7-dehydro-4,5alpha-epoxy-3,14-dihydroxy-6,7:2',3'-indolomorphinans on opioid receptor affinity, selectivity, and efficacy. J Med Chem 2001, 44, 9, 1471. |
| 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) | 33927 | (1S,5R,13R,17S)-10,17-dihydroxy-12-oxa-4-azapentacyclo[9.6.1.0(1,13).0(5,17).0(7,18)]octadeca-7(18),8,10-trien-14-one | C16H17NO4 | 详情 | 详情 | |
| (II) | 11818 | Phenyl hydrazine; 1-Phenylhydrazine | 100-63-0 | C6H8N2 | 详情 | 详情 |
| (III) | 50974 | (1S,2S,13R,21R)-14-oxa-11,22-diazaheptacyclo[13.9.1.0(1,13).0(2,21).0(4,12).0(5,10).0(19,25)]pentacosa-4(12),5,7,9,15(25),16,18-heptaene-2,16-diol | C22H20N2O3 | 详情 | 详情 | |
| (IV) | 40015 | 3-bromo-2-methyl-1-propene | 1458-98-6 | C4H7Br | 详情 | 详情 |