5-bromo-1-methoxypentyl methyl ether; 5-bromo-1,1-dimethoxypentane -Drug Synthesis Database

【结构式】

【分子编号】25645

【品名】5-bromo-1-methoxypentyl methyl ether; 5-bromo-1,1-dimethoxypentane

【CA登记号】

【分子式】C₇H₁₅BrO₂

【分子量】211.0989

【元素组成】C 39.83% H 7.16% Br 37.85% O 15.16%

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)

Alkylation of N-Boc-piperazine (I) with bromoacetal (II) provided piperazine acetal (III). This was submitted to Fisher cyclization with 4-(1,2,4-triazol-4-yl)phenyl hydrazine (IV) in aqueous H2SO4 to afford the deprotected indole (V). Wittig reaction of 3-fluorobenzaldehyde (VII) with phosphorane prepared from (methoxymethyl)phosphonium salt (VI) and PhLi furnished the methoxyvinyl compound (VIII) as an E:Z mixture. Subsequent acid hydrolysis of the enol ether function of (VIII) yielded aldehyde (IX). The target compound was then obtained by reductive alkylation of piperazine (V) with aldehyde (IX) in the presence of NaBH3CN.

参考文献中间体

合成目标

【1】 Chambers, M.S.; Goodacre, S.; Street, L.J.; et al.; 3-(Piperazinylpropyl)indoles: Selective, orally bioavailable h5-HT1D receptor agonists as potential antimigraine agents. J Med Chem 1999, 42, 4, 691.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIIa)	25650	1-fluoro-3-[(E)-2-methoxyethenyl]benzene; (E)-2-(3-fluorophenyl)ethenyl methyl ether		C₉H₉FO	详情	详情
(VIIIb)	53875	(Z)-2-(3-fluorophenyl)ethenyl methyl ether; 1-fluoro-3-[(Z)-2-methoxyethenyl]benzene	n/a	C₉H₉FO	详情	详情
(I)	13225	N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate	143238-38-4	C₉H₁₈N₂O₂	详情	详情
(II)	25645	5-bromo-1-methoxypentyl methyl ether; 5-bromo-1,1-dimethoxypentane		C₇H₁₅BrO₂	详情	详情
(III)	25646	tert-butyl 4-(5,5-dimethoxypentyl)-1-piperazinecarboxylate		C₁₆H₃₂N₂O₄	详情	详情
(IV)	25647	4-(4-hydrazinophenyl)-4H-1,2,4-triazole		C₈H₉N₅	详情	详情
(V)	25648	3-[3-(1-piperazinyl)propyl]-5-(4H-1,2,4-triazol-4-yl)-1H-indole		C₁₇H₂₂N₆	详情	详情
(VI)	25649	(methoxymethyl)(triphenyl)phosphonium bromide		C₂₀H₂₀BrOP	详情	详情
(VII)	18887	3-Fluorobenzaldehyde	456-48-4	C₇H₅FO	详情	详情
(IX)	25651	3-(3-fluorophenyl)propanal		C₉H₉FO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

5-Bromovaleryl chloride (VI) was reduced to aldehyde (VII) by means of lithium tri-tert-butoxyaluminumhydride at -78 C and subsequently converted into the dimethyl acetal (VIII) with H2SO4 in methanol (1). Alkylation of 4-hydroxypiperidine (IX) with bromoacetal (VIII) gave adduct (X). This was subjected to Fisher indolization with the hydrazine (V), yielding indole (XI). The piperidine hydroxyl group was then oxidized to the corresponding ketone (XII) using sulfur trioxide-pyridine complex in DMSO.

参考文献中间体

合成目标

【1】 Matassa, V.G.; Pengilley, R.R.; Russell, M.G.N.; et al.; 3-[3-(Piperidin-1-yl)propyl]indoles as highly selective h5-HT1D receptor agonists. J Med Chem 1999, 42, 24, 4981.
【2】 Baker, R.; Bourrain, S.; Castro Pineiro, J.L.; Chambers, M.S.; Guiblin, A.R.; Hobbs, S.C.; Jelley, R.A.; Madin, A.; Matassa, V.G.; Reeve, A.J.; Russell, M.G.N.; Showell, G.A.; Sternfeld, F.; Street, L.J.; Van Niel, M.B. (Merck Sharp & Dohme Ltd.); Azetidine, pyrrolidine and piperidine derivs.. EP 0804434; JP 1998503768; US 5854268; WO 9604274 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	25647	4-(4-hydrazinophenyl)-4H-1,2,4-triazole		C₈H₉N₅	详情	详情
(VI)	39700	5-bromopentanoyl chloride	4509-90-4	C₅H₈BrClO	详情	详情
(VII)	43094	5-bromopentanal		C₅H₉BrO	详情	详情
(VIII)	25645	5-bromo-1-methoxypentyl methyl ether; 5-bromo-1,1-dimethoxypentane		C₇H₁₅BrO₂	详情	详情
(IX)	12076	4-Piperidinol; 4-Hydroxypiperidine	5382-16-1	C₅H₁₁NO	详情	详情
(X)	43095	1-(5,5-dimethoxypentyl)-4-piperidinol		C₁₂H₂₅NO₃	详情	详情
(XI)	43096	1-[3-[5-(4H-1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]-4-piperidinol		C₁₈H₂₃N₅O	详情	详情
(XII)	43097	1-[3-[5-(4H-1,2,4-triazol-4-yl)-1H-indol-3-yl]propyl]-4-piperidinone		C₁₈H₂₁N₅O	详情	详情

Extended Information