ethyl 3-([2-amino-5-[(4-cyanobenzoyl)amino]benzoyl]amino)propanoate -Drug Synthesis Database

【结构式】

【分子编号】22351

【品名】ethyl 3-([2-amino-5-[(4-cyanobenzoyl)amino]benzoyl]amino)propanoate

【CA登记号】

【分子式】C₂₀H₂₀N₄O₄

【分子量】380.40336

【元素组成】C 63.15% H 5.3% N 14.73% O 16.82%

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：(VI)

1) Hydrogenation of 5-nitroisatoic anhydride (I) over Pd/C provided amine (II), which was acylated to amide (IV) with 4-cyanobenzoyl chloride (III). Subsequent reaction of (IV) with beta-alanine ethyl ester (V) yielded diamide (VI). The amino group of (VI) was then protected by alkylation with benzhydryl bromide (VII) yielding (VIII). Further condensation of (VIII) with bromoacetyl bromide (IX), followed by cyclization of the intermediate bromoacetamide in the presence of Cs2CO3 afforded benzodiazepinedione (X). The benzhydryl protecting group of (X) was cleaved by treatment with HF in the presence of ethyl methyl sulfide and anisole to yield (XI). The tetrazole ring of (XII) was then constructed by treatment of (XI) with trimethylsilylazide under Mitsunobu conditions. Subsequent conversion of the cyano group of (XII) into amidine was effected by the sequence of H2S addition, followed by S-methylation with CH3I to give (XIII), and then substitution of the methylthio group of (XIII) for an amino group. Finally, basic hydrolysis with LiOH provided the target carboxylic acid.

参考文献中间体

合成目标

【1】 Robarge, K.D.; Dina, M.S.; Somers, T.C.; Lee, A.; Rawson, T.E.; Olivero, A.G.; Tischler, M.H.; Webb, R.R. II; Weese, K.J.; Aliagas, I.; Blackburn, B.K.; Preparation and biological activity of novel tricyclic GPIIb/IIIa antagonists. Bioorg Med Chem 1998, 6, 12, 2345.

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)	22347	5-Nitroisatoic anhydride; 6-nitro-2H-3,1-benzoxazine-2,4(1H)-dione	4693-02-1	C₈H₄N₂O₅	详情	详情
(II)	22348	6-amino-2H-3,1-benzoxazine-2,4(1H)-dione		C₈H₆N₂O₃	详情	详情
(IV)	22350	4-cyano-N-(2,4-dioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)benzamide		C₁₆H₉N₃O₄	详情	详情
(VI)	22351	ethyl 3-([2-amino-5-[(4-cyanobenzoyl)amino]benzoyl]amino)propanoate		C₂₀H₂₀N₄O₄	详情	详情
(VII)	17639	beta-Alanine, ethyl ester; ethyl 3-aminopropanoate	924-73-2	C₅H₁₁NO₂	详情	详情
(VIII)	22353	ethyl 3-([2-(benzhydrylamino)-5-[(4-cyanobenzoyl)amino]benzoyl]amino)propanoate		C₃₃H₃₀N₄O₄	详情	详情
(X)	22355	ethyl 3-[1-benzhydryl-7-[(4-cyanobenzoyl)amino]-2,5-dioxo-1,2,3,5-tetrahydro-4H-1,4-benzodiazepin-4-yl]propanoate		C₃₅H₃₀N₄O₅	详情	详情
(XI)	22356	ethyl 3-[7-[(4-cyanobenzoyl)amino]-2,5-dioxo-1,2,3,5-tetrahydro-4H-1,4-benzodiazepin-4-yl]propanoate		C₂₂H₂₀N₄O₅	详情	详情
(XII)	22357	ethyl 3-[8-[(4-cyanobenzoyl)amino]-6-oxo-4H-[1,2,3,4]tetraazolo[1,5-a][1,4]benzodiazepin-5(6H)-yl]propanoate		C₂₂H₁₉N₇O₄	详情	详情
(XIII)	22358	ethyl 3-[8-([4-[imino(methylsulfanyl)methyl]benzoyl]amino)-6-oxo-4H-[1,2,3,4]tetraazolo[1,5-a][1,4]benzodiazepin-5(6H)-yl]propanoate		C₂₃H₂₃N₇O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 6,7-dimethoxy-4-(1-piperazinyl)quinazoline (I) with 4-bromophenylamine (II) by means of CDI or triphosgene gives the target piperazine-1-carboxamide. Alternatively, the reaction of 4-bromophenylamine (II) with 4-nitrophenyl chloroformate (III) by means of TEA gives the carbamate (IV), which is finally condensed with the quinazoline (I) in hot NMP to yield the target piperazine-1-carboxamide.

参考文献中间体

合成目标

【1】 Matsuno, K.; Ichimura, M.; Nakajima, T.; Tahara, K.; Fujiwara, S.; Kase, H.; Ushiki, J.; Giese, N.A.; Pandey, A.; Scarborough, R.M.; Lokker, N.A.; Yu, J.C.; Irie, J.; Tsukuda, E.; Ide, S.-i; Oda, S.; Nomoto, Y.; Potent and selective inhibitors of platelet-derived growth factor receptor phosphorylation. 1. Synthesis, structure-activity relationship, and biological effects of a new class of quinazoline derivatives. J Med Chem 2002, 45, 14, 3057.

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)	41610	6,7-dimethoxy-4-(1-piperazinyl)quinazoline; 6-methoxy-4-(1-piperazinyl)-7-quinazolinyl methyl ether		C₁₄H₁₈N₄O₂	详情	详情
(II)	22351	ethyl 3-([2-amino-5-[(4-cyanobenzoyl)amino]benzoyl]amino)propanoate		C₂₀H₂₀N₄O₄	详情	详情
(III)	16605	4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene	7693-46-1	C₇H₄ClNO₄	详情	详情
(IV)	63170	4-nitrophenyl 4-bromophenylcarbamate		C₁₃H₉BrN₂O₄	详情	详情

Extended Information