2-[(Z)-1-acetyl-2-(2-nitrophenyl)ethenyl]-1,3,2lambda(5)-dioxaphosphinan-2-one -Drug Synthesis Database

【结构式】

【分子编号】20574

【品名】2-[(Z)-1-acetyl-2-(2-nitrophenyl)ethenyl]-1,3,2lambda(5)-dioxaphosphinan-2-one

【CA登记号】

【分子式】C₁₃H₁₄NO₆P

【分子量】311.231062

【元素组成】C 50.17% H 4.53% N 4.5% O 30.84% P 9.95%

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：(IX)

The reaction of trimethylene glycol (I) with PCl3 gives 2-chloro-1,3,2-dioxaphosphorinane (II), which is condensed with propargyl alcohol (III) by means of triethylamine in acetonitrile to give a mixture of 2-allenyl- and 2-propargyl-2-oxo-1,3,2-dioxaphosphorinane (IV and V). The reaction of this mixture with isobutylamine in acetonitrile affords 2-(2-isobutylamino-1-propenyl)-2-oxo-1,3,2-dioxaphosphorinane (VI). The hydrolysis of the enamine (VI) with malonic acid gives 2-acetonyl-2-oxo-1,3,2-dioxaphosphorinane (VII), which is condensed with isobutyl-(2-nitrobenzylidene)amine (VIII) to yield 2-[1-(2-nitrobenzylidene)-2-oxopropyl]-2-oxo-1,3,2-dioxaphosphorinane (IX). Finally, this compound is cyclized with methyl 3-aminocrotonate (X) in refluxing acetonitrile.

参考文献中间体

合成目标

【1】 Morita, I.; Tsuda, M.; Kise, M.; Sugiyama, M.; Improved synthesis of methyl 2, 6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3, 2-dioxaphosphorinan-2-yl)-1, 4-dihydropyridine-3-carboxylate (DHP-218). Chem Pharm Bull 1988, 36, 3, 1139-42.

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)	14685	1,3-propanediol; Trimethylene Glycol	504-63-2	C₃H₈O₂	详情	详情
(II)	20567	2-chloro-1,3,2-dioxaphosphinane		C₃H₆ClO₂P	详情	详情
(III)	16664	Propargyl Alcohol; 2-propyn-1-ol	107-19-7	C₃H₄O	详情	详情
(IV)	20569	2-(1,2-propadienyl)-1,3,2lambda(5)-dioxaphosphinan-2-one		C₆H₉O₃P	详情	详情
(V)	20570	2-(1-propynyl)-1,3,2lambda(5)-dioxaphosphinan-2-one		C₆H₉O₃P	详情	详情
(VI)	20571	2-[(E)-2-(isobutylamino)-1-propenyl]-1,3,2lambda(5)-dioxaphosphinan-2-one		C₁₀H₂₀NO₃P	详情	详情
(VII)	20572	2-(2-oxopropyl)-1,3,2lambda(5)-dioxaphosphinan-2-one		C₆H₁₁O₄P	详情	详情
(VIII)	20573	2-methyl-N-[(Z)-(2-nitrophenyl)methylidene]-1-propanamine; N-isobutyl-N-[(Z)-(2-nitrophenyl)methylidene]amine		C₁₁H₁₄N₂O₂	详情	详情
(IX)	20574	2-[(Z)-1-acetyl-2-(2-nitrophenyl)ethenyl]-1,3,2lambda(5)-dioxaphosphinan-2-one		C₁₃H₁₄NO₆P	详情	详情
(X)	11372	Methyl (E)-3-amino-2-butenoate; Methyl 3-aminocrotonate		C₅H₉NO₂	详情	详情
(XI)	12963	Malonic acid	141-82-2	C₃H₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The condensation of Cyclic acetonylphosphonate (II), obtained from bromoacetone and cyclic phosphite (I) by an Arbuzov reaction, with o-nitrobenzaldehyde in the presence of piperidine - AcOH salt in boiling benzene gives benzylidene phosphonale (III), which is cyclized with methyl 3-aminocrotonate (IV) in reflux in 2-propanol affording methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2 oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4 dihydro-pyridine-3 carboxylate.

参考文献中间体

合成目标

【1】 Kimura, K.; Morita, I. (Nippon Shinyaku Co., Ltd.); 1,4-Dihydropyridine-3-carboxylate derivs.. AU 8541405; BE 0902210; EP 0159040; ES 8606276; FR 2563222; GB 2157695; JP 1985248693; US 5036059 .
【2】 Kimura, K.; DHP-218. Drugs Fut 1987, 12, 3, 212.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11370	2-Nitrobenzaldehyde	552-89-6	C₇H₅NO₃	详情	详情
	20549	1-bromoacetone	598-31-2	C₃H₅BrO	详情	详情
(I)	22929	2-methoxy-1,3,2-dioxaphosphinane		C₄H₉O₃P	详情	详情
(II)	20572	2-(2-oxopropyl)-1,3,2lambda(5)-dioxaphosphinan-2-one		C₆H₁₁O₄P	详情	详情
(III)	20574	2-[(Z)-1-acetyl-2-(2-nitrophenyl)ethenyl]-1,3,2lambda(5)-dioxaphosphinan-2-one		C₁₃H₁₄NO₆P	详情	详情

Extended Information