2-adamantanone -Drug Synthesis Database

【结构式】

【分子编号】40404

【品名】2-adamantanone

【CA登记号】700-58-3

【分子式】C₁₀H₁₄O

【分子量】150.22056

【元素组成】C 79.96% H 9.39% O 10.65%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

The condensation of adamantan-2-one (I) with 2-pyridyllithium (II) in THF/ethyl ether gives 2-(2-pyridyl)adamantan-2-ol (III), which is treated with dry HCl in ethanol to yield the pyridinium salt (IV). The hydrogenation of (IV) with H2 over PtO2 in ethanol affords 2-(2-piperidinyl)adamantan-2-ol (V), which is treated with SOCl2 in refluxing dichloromethane to provide the piperidinium chloride (VI). The dehydrochlorination of (VI) with KOH in refluxing ethanol yields the tetrahydropyridine (VIII), which is finally hydrogenated with NaBH4 in methanol.

参考文献中间体

合成目标

【1】 Foscolos, G.B.; De Clercq, E.; Kolocouris, A.; Tataridis, D.; Mavromoustalkos, T.; Fytas, G.; Synthesis of 2-(2-adamantyl)piperidines and structure anti-influenza virus a activity relationship study using a combination of NMR spectroscopy and molecular modeling. Bioorg Med Chem Lett 1999, 9, 24, 3465.

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)	40404	2-adamantanone	700-58-3	C₁₀H₁₄O	详情	详情
(II)	34016	2-pyridinyllithium		C₅H₄LiN	详情	详情
(III)	40405	2-(2-pyridinyl)-2-adamantanol		C₁₅H₁₉NO	详情	详情
(IV)	40406	2-(2-hydroxy-2-adamantyl)pyridinium chloride		C₁₅H₂₀ClNO	详情	详情
(V)	40407	2-(2-piperidinyl)-2-adamantanol		C₁₅H₂₅NO	详情	详情
(VI)	40408	2-(2-chloro-2-adamantyl)piperidinium chloride		C₁₅H₂₅Cl₂N	详情	详情
(VII)	40409	2-tricyclo[3.3.1.1(3,7)]dec-2-ylidenepiperidine		C₁₅H₂₃N	详情	详情
(VIII)	40410	6-(2-adamantyl)-2,3,4,5-tetrahydropyridine		C₁₅H₂₃N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Preparation of the intermediate aryl triflate (V) is shown is Scheme 29890101a. The dilithiated derivative of 4-bromo-3,5-dichlorophenol (I) is condensed with 2-adamantanone (II) to produce the carbinol adduct (III). Reduction of the tertiary alcohol of (III) by means of concentrated HI in boiling AcOH leads to the adamantanyl phenol (IV). This is then reacted with trifluoromethanesulfonic anhydride in cold pyridine to yield sulfonate (V).

参考文献中间体

合成目标

【1】 Paul, R.; Boigegrain, R.; Nisato, D.; Casellas, P.; Herbert, J.M.; Bourrie, B.; Bourrie, M.; Lair, P.; Vernieres, J.C. (Sanofi-Synthélabo); Benzene derivs., preparation method and pharmaceutical compsns. containing same. EP 1192122; FR 2794742; JP 2003502306; US 6482986; WO 0076953 .

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)	62827	4-bromo-3,5-dichlorophenol		C₆H₃BrCl₂O	详情	详情
(II)	40404	2-adamantanone	700-58-3	C₁₀H₁₄O	详情	详情
(III)	62828	2-(2,6-dichloro-4-hydroxyphenyl)tricyclo[3.3.1.1^3,7]decan-2-ol		C₁₆H₁₈Cl₂O₂	详情	详情
(IV)	62829	3,5-dichloro-4-tricyclo[3.3.1.1^3,7]dec-2-ylphenol		C₁₆H₁₈Cl₂O	详情	详情
(V)	62830	3,5-dichloro-4-tricyclo[3.3.1.1~3,7~]dec-2-ylphenyl trifluoromethanesulfonate		C₁₇H₁₇Cl₂F₃O₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Thionation of 2-adamantanone (I) by means of P4S10 gives thioketone (II). Subsequent addition of tert-butyl acetate to thioadamantanone (II) furnishes the beta-mercapto ester (III). After acidic cleavage of the tert-butyl ester of (III), the resultant mercapto acid (IV) is cyclized to the thiolactone (V) by using EDC. Subsequent lactone ring opening in (V) with dimethylamine gives rise to amide (VI). Finally, the thiol group of (VI) is nitrosated with tert-butyl nitrite to provide the desired nitrosothio compound.

参考文献中间体

合成目标

【1】 Lin, C.-E.; et al.; Design and synthesis of nitrosylated paclitaxel (NO-paclitaxel) and adamantanyl nitric oxide donor as antirestenosis agents. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 36.

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)	40404	2-adamantanone	700-58-3	C₁₀H₁₄O	详情	详情
(II)	58354	2-adamantanethione		C₁₀H₁₄S	详情	详情
(III)	58355	tert-butyl 2-(2-sulfanyl-2-adamantyl)acetate		C₁₆H₂₆O₂S	详情	详情
(IV)	58356	2-(2-sulfanyl-2-adamantyl)acetic acid		C₁₂H₁₈O₂S	详情	详情
(V)	58357			C₁₂H₁₆OS	详情	详情
(VI)	58358	N,N-dimethyl-2-(2-sulfanyl-2-adamantyl)acetamide		C₁₄H₂₃NOS	详情	详情

合成路线4

该中间体在本合成路线中的序号：(XI)

In an adapted method, complete solution-phase synthesis of SQ-109 is achieved by the substitution of (2E)-1-bromo-3,7-dimethylocta-2,6-diene (VIII) by ethylene diamine (IX) at –78 °C in dry DCM to give (E)-N’-(3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (X) (4, 5). Finally, amine (X) is made to undergo reductive amination with 2-adamantanone (XI) in MeOH using NaBH4 under an N2 atmosphere overnight to give SQ-109, which can be extracted with ethyl acetate or converted to a hydrochloride salt using HCl and MeOH. Scheme 2.

参考文献中间体

合成目标

【4】 Onajole, O.K., Govender, P., van Helden, P.D., Kruger, H.G., Maguire, G.E., Wiid, I., Govender, T. Synthesis and evaluation of SQ109 analogues as potential anti-tuberculosis candidates. Eur J Med Chem 2010, 45(5): 2075-9.
【5】 Onajole, O.K., Sosibo, S., Govender, P. et al. Novel linear diamine disubstituted polycyclic ‘cage’ derivatives as potential antimycobacterial candidates. Chem Biol Drug Design 2011, 78(6): 1022-30.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	31116	(2E)-1-bromo-3,7-dimethyl-2,6-octadiene; trans-Geranyl bromide; Geranyl bromide	6138-90-5	C₁₀H₁₇Br	详情	详情
(IX)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(X)	66063	(E)-N’-(3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine		C₁₂H₂₄N₂	详情	详情
(XI)	40404	2-adamantanone	700-58-3	C₁₀H₁₄O	详情	详情

Extended Information