methyl 7-cyano-4-oxo-4H-quinolizine-2-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】63675

【品名】methyl 7-cyano-4-oxo-4H-quinolizine-2-carboxylate

【CA登记号】

【分子式】C₁₂H₈N₂O₃

【分子量】228.2072

【元素组成】C 63.16% H 3.53% N 12.28% O 21.03%

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：(IV)

6-Methylnicotinonitrile (I) is oxidized by means of SeO2 in refluxing dioxane to furnish aldehyde (II). Subsequent condensation of (II) with dimethyl 2-(diethoxyphosphoryl)succinate (III) gives rise to the quinolizine derivative (IV). The cyano group of (IV) is then reduced to the primary amine (V) by catalytic hydrogenation over Pd/C. After protecting amine (V) as the corresponding N-Boc derivative (VI), alkaline hydrolysis of the methyl ester group provides acid (VII) (1). Coupling of acid (VII) with (S) t-butyl 3-amino-2-(benzenesulfonylamino)propionate (VIII) by means of HATU leads to amide (IX) (1,2).

参考文献中间体

合成目标

【1】 Rej, R.; Lamothe, S.; Zacharie, B.; Labrecque, D.; Courchesne, M.; Falardeau, G.; Abbot, S.; Wang, W.; Chan, L.; Meerovitch, K.; Bergeron, F.; Attardo, G.; Synthesis and in vitro potency of quinolizinone-based alphavbeta3 receptor antagonists. Proc Am Assoc Cancer Res 2002, 43.
【2】 Attardo, G.; Lamothe, S.; Rej, R.; Zacharie, B.; Falardeau, G.; Labrecque, D.; Courchesne, M.; Abbott, S. (Shire BioChem Inc.); Quinolizinones as integrin inhibitors. EP 1115724; US 6630488; WO 0017197 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63672	6-methylnicotinonitrile	C₇H₆N₂	详情	详情
(II)	63673	6-formylnicotinonitrile	C₇H₄N₂O	详情	详情
(III)	63674	dimethyl 2-(diethoxyphosphoryl)succinate	C₁₀H₁₉O₇P	详情	详情
(IV)	63675	methyl 7-cyano-4-oxo-4H-quinolizine-2-carboxylate	C₁₂H₈N₂O₃	详情	详情
(V)	63676	methyl 7-(aminomethyl)-4-oxo-4H-quinolizine-2-carboxylate	C₁₂H₁₂N₂O₃	详情	详情
(VI)	63677	methyl 7-{[(tert-butoxycarbonyl)amino]methyl}-4-oxo-4H-quinolizine-2-carboxylate	C₁₇H₂₀N₂O₅	详情	详情
(VII)	63678	7-{[(tert-butoxycarbonyl)amino]methyl}-4-oxo-4H-quinolizine-2-carboxylic acid	C₁₆H₁₈N₂O₅	详情	详情
(VIII)	31423	tert-butyl (2S)-3-amino-2-[(phenylsulfonyl)amino]propanoate	C₁₃H₂₀N₂O₄S	详情	详情
(IX)	63679	tert-butyl (2S)-3-{[(7-{[(tert-butoxycarbonyl)amino]methyl}-4-oxo-4H-quinolizin-2-yl)carbonyl]amino}-2-[(phenylsulfonyl)amino]propanoate	C₂₉H₃₆N₄O₈S	详情	详情

Extended Information