N-[4-(3-cyano-2-methylpropanoyl)phenyl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】29201

【品名】N-[4-(3-cyano-2-methylpropanoyl)phenyl]acetamide

【CA登记号】

【分子式】C₁₃H₁₄N₂O₂

【分子量】230.26644

【元素组成】C 67.81% H 6.13% N 12.17% O 13.9%

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：(V)

Friedel-Crafts acylation of acetanilide (I) with propionyl chloride in the presence of AlCl3 afforded 4'-(acetamido)propiophenone (II). Subsequent Mannich reaction of (II) with dimethylamine hydrochloride and formaldehyde produced the aminoketone (III). Quaternization of the tertiary amine of (III) with MeI, followed by displacement of the resulting ammonium salt (IV) with KCN yielded the intermediate ketonitrile (V). In alternative procedure, nitrile (V) was prepared by acylation of acetanilide (I) with 3-chloro-2-methylpropionyl chloride, and further displacement of the resulting beta-chloroketone (VI) with KCN. Acid hydrolysis of both nitrile and acetamido groups of (V) provided ketoacid (VII), which was cyclized with hydrazine to give pyridazinone (VIII). Finally, acylation of the amino group of (VIII) by means of pyridine-2-carbonyl chloride furnished the title amide.

参考文献中间体

合成目标

【1】 Liu, C.M.; et al.; Synthesis and platelet aggregation inhibitory activity of 6-(4'-substituted acylaminophenyl)-4,5-dihydro-3-(2H)-pyridazinones. Acta Pharm Sin 1999, 34, 1, 23.

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)	10194	N-Phenylacetamide; Acetanilide	103-84-4	C₈H₉NO	详情	详情
(II)	29198	N-(4-propionylphenyl)acetamide		C₁₁H₁₃NO₂	详情	详情
(III)	29199	N-[4-[3-(dimethylamino)-2-methylpropanoyl]phenyl]acetamide		C₁₄H₂₀N₂O₂	详情	详情
(IV)	29200	3-[4-(acetamido)phenyl]-N,N,N,2-tetramethyl-3-oxo-1-propanaminium iodide		C₁₅H₂₃IN₂O₂	详情	详情
(V)	29201	N-[4-(3-cyano-2-methylpropanoyl)phenyl]acetamide		C₁₃H₁₄N₂O₂	详情	详情
(VI)	29202	N-[4-(3-chloro-2-methylpropanoyl)phenyl]acetamide		C₁₂H₁₄ClNO₂	详情	详情
(VII)	29203	4-(4-aminophenyl)-3-methyl-4-oxobutyric acid		C₁₁H₁₃NO₃	详情	详情
(VIII)	29204	6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone		C₁₁H₁₃N₃O	详情	详情
(IX)	29205	2-pyridinecarbonyl chloride		C₆H₄ClNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Friedel-Crafts acylation of acetanilide (I) with propionyl chloride in the presence of AlCl3 afforded 4'-(acetamido)propiophenone (II). Subsequent Mannich reaction of (II) with dimethylamine hydrochloride and formaldehyde produced the aminoketone (III). Quaternization of the tertiary amine of (III) with MeI, followed by displacement of the resulting ammonium salt (IV) with KCN yielded the intermediate ketonitrile (V). In alternative procedure, nitrile (V) was prepared by acylation of acetanilide (I) with 3-chloro-2-methylpropionyl chloride, and further displacement of the resulting alpha-chloroketone (VI) with KCN. Acid hydrolysis of both nitrile and acetamido groups of (V) provided ketoacid (VII), which was cyclized with hydrazine to give pyridazinone (VIII). Finally, acylation of the amino group of (VIII) by means of pyridine-4-carbonyl chloride furnished the title amide.

参考文献中间体

合成目标

【1】 Liu, C.M.; et al.; Synthesis and platelet aggregation inhibitory activity of 6-(4'-substituted acylaminophenyl)-4,5-dihydro-3-(2H)-pyridazinones. Acta Pharm Sin 1999, 34, 1, 23.

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)	10194	N-Phenylacetamide; Acetanilide	103-84-4	C₈H₉NO	详情	详情
(II)	29198	N-(4-propionylphenyl)acetamide		C₁₁H₁₃NO₂	详情	详情
(III)	29199	N-[4-[3-(dimethylamino)-2-methylpropanoyl]phenyl]acetamide		C₁₄H₂₀N₂O₂	详情	详情
(IV)	29200	3-[4-(acetamido)phenyl]-N,N,N,2-tetramethyl-3-oxo-1-propanaminium iodide		C₁₅H₂₃IN₂O₂	详情	详情
(V)	29201	N-[4-(3-cyano-2-methylpropanoyl)phenyl]acetamide		C₁₃H₁₄N₂O₂	详情	详情
(VI)	29202	N-[4-(3-chloro-2-methylpropanoyl)phenyl]acetamide		C₁₂H₁₄ClNO₂	详情	详情
(VII)	29203	4-(4-aminophenyl)-3-methyl-4-oxobutyric acid		C₁₁H₁₃NO₃	详情	详情
(VIII)	29204	6-(4-aminophenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone		C₁₁H₁₃N₃O	详情	详情
(IX)	27850	isonicotinoyl chloride	39178-35-3	C₆H₄ClNO	详情	详情

Extended Information