(1aR,10bS)-6-bromo-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cycloheptene -Drug Synthesis Database

【结构式】

【分子编号】56208

【品名】(1aR,10bS)-6-bromo-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cycloheptene

【CA登记号】

【分子式】C₁₆H₁₁BrF₂

【分子量】321.1641464

【元素组成】C 59.84% H 3.45% Br 24.88% F 11.83%

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：(XII)

Reaction of alcohol (IV) with 48% HBr or with PBr3 affords the anti-bromo derivative (XII), which is condensed with pyrazine (XIII) in refluxing acetonitrile to give anti-1-[10,11-(difluoromethano)dibenzosuber-5-yl]pyrazinium bromide (XIV). Reduction of compound (XIV) with NaBH4 in ethyl acetate provides the piperazine derivative (VIII), which is finally condensed with 5-[2(R),3-epoxypropoxy]quinoline (IX) obtained by reaction of 5-hydroxyquinoline (X) with (R)-glycidyl 4-nitrobenzene- sulfonate (XV) by means of K2CO3 in DMF in hot ethanol.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Silvestre, J.S.; Bayes, M.; Zosuquidar Trihydrochloride.. Drugs Fut 2003, 28, 2, 125-136.
【2】 Le Tourneau, M.E.; Wilson, T.M.; Huff, B.E.; Bush, J.K.; Reutzel-Edens, S.M. (Eli Lilly and Company); Process for preparing 10,11-methanobenzosuberane derivs.. WO 0075121 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	56204	(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-ol		C₁₆H₁₂F₂O	详情	详情
(VIII)	56207	1-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]piperazine		C₂₀H₂₀F₂N₂	详情	详情
(IX)	56211	(2R)oxiranylmethyl 5-quinolinyl ether; 5-[(2R)oxiranylmethoxy]quinoline		C₁₂H₁₁NO₂	详情	详情
(X)	23805	5-quinolinol	578-67-6	C₉H₇NO	详情	详情
(XII)	56208	(1aR,10bS)-6-bromo-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cycloheptene		C₁₆H₁₁BrF₂	详情	详情
(XIII)	56209	pyrazine		C₄H₄N₂	详情	详情
(XIV)	56210	1-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]pyrazin-1-ium bromide		C₂₀H₁₅BrF₂N₂	详情	详情
(XV)	56212	(2R)oxiranylmethyl 3-nitrobenzenesulfonate		C₉H₉NO₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

Condensation of the anti-bromo derivative (XII) with piperazine (XVI) in refluxing acetonitrile provides 1-[10,11-(difluoromethano)dibenzosuber-5-yl]piperazine as a mixture of syn- and anti-isomers (XVII), which is separated by crystallization. Finally, the desired anti-isomer (VIII) is condensed with 5-[2(R),3-epoxypropoxy]quinoline (IX) in hot ethanol.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Silvestre, J.S.; Bayes, M.; Zosuquidar Trihydrochloride.. Drugs Fut 2003, 28, 2, 125-136.
【2】 Barnett, C.J.; Wilson, T.M.; Astleford, B.A.; Kobierski, M.E. (Eli Lilly and Company); Process for preparing a 10,11-methanodibenzosuberane deriv.. WO 0075132 .

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)	56207	1-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]piperazine		C₂₀H₂₀F₂N₂	详情	详情
(IX)	56211	(2R)oxiranylmethyl 5-quinolinyl ether; 5-[(2R)oxiranylmethoxy]quinoline		C₁₂H₁₁NO₂	详情	详情
(XII)	56208	(1aR,10bS)-6-bromo-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cycloheptene		C₁₆H₁₁BrF₂	详情	详情
(XVI)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(XVII)	59523	1-[(1aR,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]piperazine		C₂₀H₂₀F₂N₂	详情	详情

Extended Information