[4-(3-chloropropoxy)phenyl](cyclopropyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】62998

【品名】[4-(3-chloropropoxy)phenyl](cyclopropyl)methanone

【CA登记号】

【分子式】C₁₃H₁₅ClO₂

【分子量】238.7136

【元素组成】C 65.41% H 6.33% Cl 14.85% O 13.4%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(IV)

Cyclization of 4-chloro-4'-hydroxybutyrophenone (I) in the presence of 50% aqueous NaOH produces cyclopropyl (4-hydroxyphenyl) ketone (II). This is then alkylated with 1-bromo-3-chloropropane (III) to afford the chloropropyl ether (IV). Chloride displacement in (IV) with an excess of piperazine (V) in the presence of KI and K2CO3 furnishes the monosubstituted piperazine (VI). Subsequent coupling of piperazine (VI) with N-Boc-L-alanine (VII) leads to amide (VIII). Finally, Boc group cleavage in (VIII) employing trifluoroacetic acid yields the title compound (1-3).

参考文献中间体

合成目标

【1】 Faghih, R.; Dwight, W.; Black, L.; Liu, H.; Gentles, R.; Phelan, K.; Esbenshade, T.A.; Ireland, L.; Miller, T.R.; Kang, C.-H.; Krueger, K.M.; Fox, G.B.; Hancock; Bennani, Y.L.; Structure-activity relationships of non-imidazole H(3) receptor ligands. Part 2: Binding preference for D-amino acids motifs. Bioorg Med Chem Lett 2002, 12, 15, 2035.
【2】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. WO 0166534 .
【3】 Black, L.A.; Faghih, R.; Bennani, Y.L.; Liu, H.; Zhang, H.Q.; Dwight, W.J.; Gentles, R.G.; Phelan, K.M.; Vasudevan, A. (Abbott Laboratories Inc.); Cyclic and bicyclic diamino histamine-3 receptor antagonists. US 2001049367; US 6559140 .

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)	62995			C₁₀H₁₁ClO₂	详情	详情
(II)	27425	cyclopropyl(4-hydroxyphenyl)methanone		C₁₀H₁₀O₂	详情	详情
(III)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(IV)	62998	[4-(3-chloropropoxy)phenyl](cyclopropyl)methanone		C₁₃H₁₅ClO₂	详情	详情
(V)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(VI)	62996			C₁₇H₂₄N₂O₂	详情	详情
(VII)	15859	Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid	7764-95-6	C₈H₁₅NO₄	详情	详情
(VIII)	64059	tert-butyl (1R)-2-(4-{3-[4-(cyclopropylcarbonyl)phenoxy]propyl}-1-piperazinyl)-1-methyl-2-oxoethylcarbamate		C₂₅H₃₇N₃O₅	详情	详情

Extended Information