　 -Drug Synthesis Database

【结构式】

【分子编号】63042

【品名】　

【CA登记号】

【分子式】C₂₈H₂₃ClN₂O₂

【分子量】454.9556

【元素组成】C 73.92% H 5.1% Cl 7.79% N 6.16% O 7.03%

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：(VIII)

Intramolecular cyclization of p-hydroxy-4-chlorobutyrophenone (I) under alkaline conditions yields cyclopropyl(4-hydroxyphenyl) ketone (II). The phenolic hydroxyl group is then alkylated by 1-bromo-3-chloropropane (III) to furnish the chloropropyl ether (IV). Subsequent condensation of alkyl chloride (IV) with piperazine (V) gives rise to the N-substituted piperazine (VI). This is then coupled with N-Boc-L-alanine (VII) in the presence of EDC/DMAP to afford amide (VIII) (1, 2). After acidic cleavage of the N-Boc protecting group, the resultant monosubstituted piperazine (IX) is acylated by furanoyl chloride (X) to furnish the target furamide derivative

参考文献中间体

合成目标

【1】 Black, L.A.; Faghih, R.; Liu, H.; et al.; Acyl-D-alanine amides: Selective histamine H3 receptor antagonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 323.
【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)	62988	5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine		C₁₁H₈BrN₅	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)	63042			C₂₈H₂₃ClN₂O₂	详情	详情
(IX)	63043			C₁₇H₁₅ClN₂O₂	详情	详情
(X)	26093	2-Furoyl chloride	527-69-5	C₅H₃ClO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Acylation of the 2-aminobenzophenone (I) with bromoacetyl bromide (II) provides the bromoacetamide (III). Subsequent treatment of (III) with ammonia leads to the benzodiazepinone (IV). Methylation of the lactam N with iodomethane in the presence of K2CO3 gives rise to (V). The potassium enolate of benzodiazepinone (V) is then alkylated by 2-(bromomethyl)naphthalene (VI) to furnish the naphthylmethyl derivative (VII). Finally, methyl ether cleavage using AlBr3 in ethanethiol provides the target phenolic compound

参考文献中间体

合成目标

【1】 Kim, K.; Volkman, S.K.; Ellman, J.A.; Synthesis of 3-substituted 1,4-benzodiazepin-2-ones. J Braz Chem Soc 1998, 9, 4, 375.

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)	63044			C₁₄H₁₂ClNO₂	详情	详情
(II)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(III)	63045			C₁₆H₁₃BrClNO₃	详情	详情
(IV)	63046			C₁₆H₁₃ClN₂O₂	详情	详情
(V)	63043			C₁₇H₁₅ClN₂O₂	详情	详情
(VI)	35612	2-(bromomethyl)naphthalene	939-26-4	C₁₁H₉Br	详情	详情
(VII)	63042			C₂₈H₂₃ClN₂O₂	详情	详情

Extended Information