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【结 构 式】 
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【分子编号】54430 【品名】(1R,10R)-17-(2-propynyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2,4,6-trien-4-ol 【CA登记号】 |
【 分 子 式 】C19H23NO 【 分 子 量 】281.39776 【元素组成】C 81.1% H 8.24% N 4.98% O 5.69% |
合成路线1
该中间体在本合成路线中的序号：(III)This compound has been obtained by two related ways: The demethylation of levorphanol (I) by the deGraw and Engstrom procedure (ethyl chloroformate and K2CO3 in refluxing chloroform and hydrolysis with NaOH) gives norlevorphanol (II), which is alkylated with propargyl bromide (III) and K2CO3 in hot DMF to yield the N-propargyl derivative (IV). The hydrostannylation of (IV) with HSnBu3 and Et3B in THF affords a mixture of the trans-(V) and cis-(VI) tributyltin precursors that are separated by column chromatography. Finally, the desired trans-isomer (V) is iodinated with I2 in CHCl3 to provide the target iodoallyl morphinan derivative. Alternatively, the hydrostannylation of propargyl alcohol (VI) by conventional methods gives the (E)-3-(tributylastannyl)allyl alcohol (VII), which is treated with CCl4 and PPh3 to yield the corresponding allyl bromide (VIII). Finally, the N-alkylation of norlevorphanol (II) with the allyl bromide (VIII) affords the already reported trans-(tributylstannyl)precursor (V).
| 【1】 Neumeyer, J.L.; Negus, S.S.; Mello, N.K.; Cohen, D.J.; Gu, X.-H.; Rusovici, D.E.; DeNunzio, N.J.; van Vliet, L.A.; Bidlack, J.M.; Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine abuse: Synthesis and opioid receptor binding affinity of N-substituted derivatives of morphinan. Bioorg Med Chem Lett 2001, 11, 20, 2735. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 | |
| (I) | 43741 | (1R,9R,10R)-17-methyl-17-azatetracyclo[7.5.3.0(1,10).0(2,7)]heptadeca-2,4,6-trien-4-ol | C17H23NO | 详情 | 详情 | |
| (II) | 43742 | (1R,9R,10R)-17-azatetracyclo[7.5.3.0(1,10).0(2,7)]heptadeca-2,4,6-trien-4-ol | C16H21NO | 详情 | 详情 | |
| (III) | 54430 | (1R,10R)-17-(2-propynyl)-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2,4,6-trien-4-ol | C19H23NO | 详情 | 详情 | |
| (IV) | 54431 | (1R,10R)-17-[(E)-3-(tributylstannyl)-2-propenyl]-17-azatetracyclo[7.5.3.0~1,10~.0~2,7~]heptadeca-2,4,6-trien-4-ol | C31H51NOSn | 详情 | 详情 | |
| (V) | 54432 | (1R,10R)-17-[(Z)-3-(tributylstannyl)-2-propenyl]-17-azatetracyclo[7.5.3.0~1,10~.0~2,7~]heptadeca-2,4,6-trien-4-ol | C31H51NOSn | 详情 | 详情 | |
| (VI) | 16664 | Propargyl Alcohol; 2-propyn-1-ol | 107-19-7 | C3H4O | 详情 | 详情 |
| (VII) | 52942 | (E)-3-(tributylstannyl)-2-propen-1-ol | n/a | C15H32OSn | 详情 | 详情 |
| (VIII) | 50995 | tributyl[(E)-3-chloro-1-propenyl]stannane | C15H31ClSn | 详情 | 详情 |