4-(4-chlorophenyl)-4-oxobutyric acid -Drug Synthesis Database

【结构式】

【分子编号】37461

【品名】4-(4-chlorophenyl)-4-oxobutyric acid

【CA登记号】3984-34-7

【分子式】C₁₀H₉ClO₃

【分子量】212.63236

【元素组成】C 56.49% H 4.27% Cl 16.67% O 22.57%

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：(III)

The reaction of p-chlorobenzaldehyde (I) sodium cyanide and ethyl acetate gives ethyl 4-(p-chlorophenyl)-4-oxobutyrate (II), which is hydrolyzed with KOH to the corresponding free acid (III). The reduction of (III) with Zn and aqueous HCl affords 4-(p-chlorophenyl)butyric acid (IV), which is condensed with heptylamine (B) by means of oxalyl chloride (A) in refluxing benzene to yield N-heptyl-4-(p-chlorophenyl)butyramide (V), which is reduced with diborane in refluxing THF to afford N-heptyl-4-(p-chlorophenyl)butylamine (VI). The acetylation of (VI) with acetyl chloride (C) by means of Na2CO3 in acetone gives N-acetyl-N-heptyl-4-(p-chlorophenyl)butylamine (VII), which is reduced with diborane as before to yield N-ethyl-N-heptyl-4-(p-chlorophenyl)butylamine (VIII). The quaternization of (VIII) with refluxing ethyl bromide (D) gives N,N-diethyl-N-heptyl-4-(p-chlorophenyl)butylammonium bromide (IX), which by elution through a column with Dowex 1-X8, hydroxide form, resin is converted into N,N-diethyl-N-heptyl-4-(p-chlorophenyl)butyl ammonium hydroxide (X). Finally, this compound is salified with diluted aqueous phosphoric acid.

参考文献中间体

合成目标

【1】 Molloy, B.B.; Steinberg, M.I.; EP 0002604 .
【2】 Hillier, K.; Castaner, J.; Clofilium Phosphate. Drugs Fut 1981, 6, 12, 764.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	23252	1-heptanamine; heptylamine	111-68-2	C₇H₁₇N	详情	详情
(A)	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(D)	30344	1-bromoethane；ethyl bromide	74-96-4	C₂H₅Br	详情	详情
(I)	29029	4-chlorobenzaldehyde	104-88-1	C₇H₅ClO	详情	详情
(II)	37460	ethyl 4-(4-chlorophenyl)-4-oxobutanoate		C₁₂H₁₃ClO₃	详情	详情
(III)	37461	4-(4-chlorophenyl)-4-oxobutyric acid	3984-34-7	C₁₀H₉ClO₃	详情	详情
(IV)	37462	4-(4-chlorophenyl)butyric acid		C₁₀H₁₁ClO₂	详情	详情
(V)	37463	4-(4-chlorophenyl)-N-heptylbutanamide		C₁₇H₂₆ClNO	详情	详情
(VI)	37464	N-[4-(4-chlorophenyl)butyl]-1-heptanamine; N-[4-(4-chlorophenyl)butyl]-N-heptylamine		C₁₇H₂₈ClN	详情	详情
(VII)	37465	N-[4-(4-chlorophenyl)butyl]-N-heptylacetamide		C₁₉H₃₀ClNO	详情	详情
(VIII)	37466	N-[4-(4-chlorophenyl)butyl]-N-ethyl-N-heptylamine; N-[4-(4-chlorophenyl)butyl]-N-ethyl-1-heptanamine		C₁₉H₃₂ClN	详情	详情
(IX)	37467	N-[4-(4-chlorophenyl)butyl]-N,N-diethyl-1-heptanaminium bromide		C₂₁H₃₇BrClN	详情	详情
(X)	37468	N-[4-(4-chlorophenyl)butyl]-N,N-diethyl-1-heptanaminium hydroxide		C₂₁H₃₈ClNO	详情	详情
(C)	19273	acetyl chloride	75-36-5	C₂H₃ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of carboxylic acid (I) with dipropylamine (II) in the presence of ethyl 1,2-dihydro-2-ethoxy-1-quinolinecarboxylate (EEDQ) yields amide (III), which is then brominated with Br2 in CCl4 to provide derivative (IV). Finally, bromoketoamide (IV) is cyclized with to 3-methyl-2-aminopyridine (V) in DMF to furnish the target product.

参考文献中间体

合成目标

【1】 Biggio, G.; Carotti, A.; Trapani, G.; Liso, G.; Sanna, E.; Serra, M.; Ricciardi, L.; Franco, M.; latrofa, A.; Novel 2-phenylimidazo[1,2-a]pyridine derivatives as potent and selective ligands for peripheral benzodiazepine receptors: Synthesis, binding affinity, and in vivo studies. J Med Chem 1999, 42, 19, 3934.

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)	37461	4-(4-chlorophenyl)-4-oxobutyric acid	3984-34-7	C₁₀H₉ClO₃	详情	详情
(II)	21856	N,N-dipropylamine; N-propyl-1-propanamine	142-84-7	C₆H₁₅N	详情	详情
(III)	47011	4-(4-chlorophenyl)-4-oxo-N,N-dipropylbutanamide		C₁₆H₂₂ClNO₂	详情	详情
(IV)	47012	3-bromo-4-(4-chlorophenyl)-4-oxo-N,N-dipropylbutanamide		C₁₆H₂₁BrClNO₂	详情	详情
(V)	13016	3-Methyl-2-pyridinylamine; 3-Methyl-2-pyridinamine; 2-Amino-3-picoline; 2-Amino-3-methylpyridine	1603-40-3	C₆H₈N₂	详情	详情

Extended Information