3-amino-3-methyl-2-piperidinone -Drug Synthesis Database

【结构式】

【分子编号】31026

【品名】3-amino-3-methyl-2-piperidinone

【CA登记号】

【分子式】C₆H₁₂N₂O

【分子量】128.17416

【元素组成】C 56.23% H 9.44% N 21.86% O 12.48%

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：(VII)

The esterification of 2-aminopropionic acid (I) with SOCl2 and methanol gives the methyl ester (II), whih is treated with benzaldehyde and TEA in dichloromethane yielding the benzylideneimine (III). The alkylation of (III) with N-(3-iodopropyl)phthalimide (IV) by means of LDA in THF affords the substituted pentanoate (V), which is treated with 1N HCl to give 2-amino-2-methyl-5-(phthalimido)pentanoic acid methyl ester (VI). The cyclization of (VI) by means of hydrazine and sodium methoxide in methanol yields the racemic 3-amino-3-methylpiperidin-2-one (VII), which is submitted to optical resolution with optically active binaphthyl phosphoric acid to afford 3(R)-amino-3-methy-piperidin-2-one (VIII). The reaction of (VIII) with 4-nitrophthalic anhydride (IX) in dioxane gives the amide (X), which is heated under vacuum to give the phthalimide (XI). The oxidation of (XI) with mCPBA in carbon tetrachloride yields the piperidinedione (XII), which is finally reduced at the nitro group by the usual methods.

参考文献中间体

合成目标

【1】 Miyachi, H.; Koiso, Y.; Shirai, R.; Niwayama, S.; Liu, J.O.; Hashimoto, Y.; Tumor necrosis factor-alpha production enhancing activity of substituted 3'-methylthalidomide: Influence of substituents at the phthaloyl moiety on the activity and stereoselectivity. Chem Pharm Bull 1998, 46, 7, 1165.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(I)	31032	alanine	302-72-7	C₃H₇NO₂	详情	详情
(II)	25315	methyl 2-aminopropanoate; Alanine, methyl ester	7625-53-8	C₄H₉NO₂	详情	详情
(III)	31022	methyl 2-[[(E)-benzylidene]amino]propanoate		C₁₁H₁₃NO₂	详情	详情
(IV)	31023	2-(3-iodopropyl)-1H-isoindole-1,3(2H)-dione		C₁₁H₁₀INO₂	详情	详情
(V)	31024	methyl 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-methyl-2-[[(E)-benzylidene]amino]pentanoate		C₂₂H₂₂N₂O₄	详情	详情
(VI)	31025	methyl 2-amino-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-methylpentanoate		C₁₅H₁₈N₂O₄	详情	详情
(VII)	31026	3-amino-3-methyl-2-piperidinone		C₆H₁₂N₂O	详情	详情
(VIII)	31027	(3R)-3-amino-3-methyl-2-piperidinone		C₆H₁₂N₂O	详情	详情
(IX)	31028	5-nitro-2-benzofuran-1,3-dione	5466-84-2	C₈H₃NO₅	详情	详情
(X)	31029	2-([[(3R)-3-methyl-2-oxopiperidinyl]amino]carbonyl)-5-nitrobenzoic acid		C₁₄H₁₅N₃O₆	详情	详情
(XI)	31030	2-[(3R)-3-methyl-2-oxopiperidinyl]-5-nitro-1H-isoindole-1,3(2H)-dione		C₁₄H₁₃N₃O₅	详情	详情
(XII)	31031	2-[(3R)-3-methyl-2,6-dioxopiperidinyl]-5-nitro-1H-isoindole-1,3(2H)-dione		C₁₄H₁₁N₃O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The esterification of 2-aminopropionic acid (I) with SOCl2 and methanol gives the methyl ester (II), whih is treated with benzaldehyde and TEA in dichloromethane yielding the benzylideneimine (III). The alkylation of (III) with N-(3-iodopropyl)phthalimide (IV) by means of LDA in THF affords the substituted pentanoate (V), which is treated with 1N HCl to give 2-amino-2-methyl-5-(phthalimido)pentanoic acid methyl ester (VI). The cyclization of (VI) by means of hydrazine and sodium methoxide in methanol yields the racemic 3-amino-3-methylpiperidin-2-one (VII), which is submitted to optical resolution with optically active binaphthyl phosphoric acid to afford 3(S)-amino-3-methylpiperidin-2-one (VIII). The reaction of (VIII) with 4-nitrophthalic anhydride (IX) in dioxane gives the amide (X), which is heated under vacuum to give the phthalimide (XI). The oxidation of (XI) with mCPBA in carbon tetrachloride yields the piperidinedione (XII), which is finally reduced at the nitro group by the usual methods.

参考文献中间体

合成目标

【1】 Miyachi, H.; Koiso, Y.; Shirai, R.; Niwayama, S.; Liu, J.O.; Hashimoto, Y.; Tumor necrosis factor-alpha production enhancing activity of substituted 3'-methylthalidomide: Influence of substituents at the phthaloyl moiety on the activity and stereoselectivity. Chem Pharm Bull 1998, 46, 7, 1165.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(I)	31032	alanine	302-72-7	C₃H₇NO₂	详情	详情
(II)	25315	methyl 2-aminopropanoate; Alanine, methyl ester	7625-53-8	C₄H₉NO₂	详情	详情
(III)	31022	methyl 2-[[(E)-benzylidene]amino]propanoate		C₁₁H₁₃NO₂	详情	详情
(IV)	31023	2-(3-iodopropyl)-1H-isoindole-1,3(2H)-dione		C₁₁H₁₀INO₂	详情	详情
(V)	31024	methyl 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-methyl-2-[[(E)-benzylidene]amino]pentanoate		C₂₂H₂₂N₂O₄	详情	详情
(VI)	31025	methyl 2-amino-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-methylpentanoate		C₁₅H₁₈N₂O₄	详情	详情
(VII)	31026	3-amino-3-methyl-2-piperidinone		C₆H₁₂N₂O	详情	详情
(VIII)	31033	(3S)-3-amino-3-methyl-2-piperidinone		C₆H₁₂N₂O	详情	详情
(IX)	31028	5-nitro-2-benzofuran-1,3-dione	5466-84-2	C₈H₃NO₅	详情	详情
(X)	31034	2-([[(3S)-3-methyl-2-oxopiperidinyl]amino]carbonyl)-5-nitrobenzoic acid		C₁₄H₁₅N₃O₆	详情	详情
(XI)	31035	2-[(3S)-3-methyl-2-oxopiperidinyl]-5-nitro-1H-isoindole-1,3(2H)-dione		C₁₄H₁₃N₃O₅	详情	详情
(XII)	31036	2-[(3S)-3-methyl-2,6-dioxopiperidinyl]-5-nitro-1H-isoindole-1,3(2H)-dione		C₁₄H₁₁N₃O₆	详情	详情

Extended Information