(1R,9R,10R)-17-azatetracyclo[7.5.3.0(1,10).0(2,7)]heptadeca-2,4,6-trien-4-ol -Drug Synthesis Database

【结构式】

【分子编号】43742

【品名】(1R,9R,10R)-17-azatetracyclo[7.5.3.0(1,10).0(2,7)]heptadeca-2,4,6-trien-4-ol

【CA登记号】

【分子式】C₁₆H₂₁NO

【分子量】243.34888

【元素组成】C 78.97% H 8.7% N 5.76% O 6.57%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

The N-dealkylation of levorphanol (I) by means of phenyl chloroformate gave rise to (-)-3-hydroxymorphinan (II). This was then condensed with cyclobutanecarbonyl chloride (III) to afford the diacyl derivative (IV). The reduction of the amide group of (IV), with concomitant ester cleavage, by means of LiAlH4 furnished the desired compound, which was finally isolated as the mandelate salt.

参考文献中间体

合成目标

【1】 Cohen, D.J.; Mello, N.K.; Zong, R.; Gao, P.; Bidlack, J.M.; Negus, S.S.; Bakthavachalam, V.; Neumeyer, J.L.; Synthesis and opioid receptor affinity of morphinan and benzomorphan derivatives: Mixed kappa agonists and mu agonists/antagonists as potential pharmacotherapeutics for cocaine dependence. J Med Chem 2000, 43, 1, 114.
【2】 Gates, M.D. Jr.; N-Cyclopropylmethyl- and -cyclobutylmethyl-morphinans. US 3285922 .

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)	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)	18589	cyclobutanecarbonyl chloride	5006-22-4	C₅H₇ClO	详情	详情
(IV)	43743	(1R,9R,10R)-17-(cyclobutylcarbonyl)-17-azatetracyclo[7.5.3.0(1,10).0(2,7)]heptadeca-2,4,6-trien-4-yl cyclobutanecarboxylate		C₂₆H₃₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

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).

参考文献中间体

合成目标

【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[7.5.3.0^1,10.0^2,7]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

Extended Information