[4'-(3-chloropropoxy)[1,1'-biphenyl]-4-yl](4-morpholinyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】63285

【品名】[4'-(3-chloropropoxy)[1,1'-biphenyl]-4-yl](4-morpholinyl)methanone

【CA登记号】

【分子式】C₂₀H₂₂ClNO₃

【分子量】359.85232

【元素组成】C 66.76% H 6.16% Cl 9.85% N 3.89% O 13.34%

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：(VIII)

Fischer esterification of 4'-hydroxybiphenyl-4-carboxylic acid (I) with H2SO4/MeOH provides ester (II). The phenolic hydroxyl group is then alkylated with 1-bromo-3-chloropropane (III) in the presence of K2CO3 to furnish the chloropropyl ether (IV). Saponification of methyl ester (IV) with LiOH leads to carboxylic acid (V), which is further activated as the corresponding acid chloride (VI) upon heating in SOCl2. Acid chloride (VI) is subsequently coupled with morpholine (VII) to yield amide (VIII). Finally, alkyl chloride (VIII) is displaced with (R,R)-2,5-dimethylpyrrolidine (IX) in the presence of K2CO3 and KI to furnish the title compound.

参考文献中间体

合成目标

【1】 Faghih, R.; Bennani, Y.L. (Abbott Laboratories Inc.); Aminoalkoxybiphenyl carboxamides as histamine-3 receptor ligands and their therapeutic applications. US 6316475; WO 0240461 .
【2】 Faghih, R.; Bennani, Y.; Aminoalkoxybiphenylcarboxamides as histamine-3 receptor ligands and their therapeutic applications. US 2002111340 .

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)	63280	4'-hydroxy[1,1'-biphenyl]-4-carboxylic acid		C₁₃H₁₀O₃	详情	详情
(II)	63281	methyl 4'-hydroxy[1,1'-biphenyl]-4-carboxylate		C₁₄H₁₂O₃	详情	详情
(III)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(IV)	63282	methyl 4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carboxylate		C₁₇H₁₇ClO₃	详情	详情
(V)	63283	4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carboxylic acid		C₁₆H₁₅ClO₃	详情	详情
(VI)	63284	4'-(3-chloropropoxy)[1,1'-biphenyl]-4-carbonyl chloride		C₁₆H₁₄Cl₂O₂	详情	详情
(VII)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(VIII)	63285	[4'-(3-chloropropoxy)[1,1'-biphenyl]-4-yl](4-morpholinyl)methanone		C₂₀H₂₂ClNO₃	详情	详情
(IX)	63286	(2R,5R)-2,5-dimethylpyrrolidine		C₆H₁₃N	详情	详情

Extended Information