methyl (2S)-2-({4-[2-(2,4-diamino-6-quinazolinyl)ethynyl]benzoyl}amino)-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanoate -Drug Synthesis Database

【结构式】

【分子编号】65107

【品名】methyl (2S)-2-({4-[2-(2,4-diamino-6-quinazolinyl)ethynyl]benzoyl}amino)-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanoate

【CA登记号】

【分子式】C₃₁H₂₆N₆O₅

【分子量】562.58488

【元素组成】C 66.18% H 4.66% N 14.94% O 14.22%

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：(VIII)

Condensation between phthaloyl ornithine methyl ester (V) and 4-iodobenzoic acid (VI), via activation with isobutyl chloroformate, furnishes the iodobenzamide (VII). Subsequent coupling of iodo amide (VII) with the ethynyl quinazoline (IV) employing Pd(PPh3)4 and CuI leads to the disubstituted acetylene (VIII). Catalytic hydrogenation of the triple bond in the presence of Pd/C affords (IX). Then, basic hydrolysis of phthalimido ester (IX) by means of Ba(OH)2 produces the target compound.

参考文献中间体

合成目标

【1】 Vaidya, C.M.; Wright, J.E.; Rosowsky, A.; Synthesis and in vitro antitumor activity of new deaza analogues of the nonpolyglutamatable antifolate Nalpha-(4-amino-4-deoxypteroyl)-Nalpha-hemiphtaloyl-L-ornithine (PT523). J Med Chem 2002, 45, 8, 1690.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	65104	2-amino-6-ethynyl-4-quinazolinylamine; 6-ethynyl-2,4-quinazolinediamine		C₁₀H₈N₄	详情	详情
(V)	42875	methyl (2S)-2-amino-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanoate		C₁₄H₁₆N₂O₄	详情	详情
(VI)	53872	4-iodobenzoic acid	619-58-9	C₇H₅IO₂	详情	详情
(VII)	65108	methyl (2S)-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-[(4-iodobenzoyl)amino]pentanoate		C₂₁H₁₉IN₂O₅	详情	详情
(VIII)	65107	methyl (2S)-2-({4-[2-(2,4-diamino-6-quinazolinyl)ethynyl]benzoyl}amino)-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanoate		C₃₁H₂₆N₆O₅	详情	详情
(IX)	65106	methyl (2S)-2-({4-[2-(2,4-diamino-6-quinazolinyl)ethyl]benzoyl}amino)-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentanoate		C₃₁H₃₀N₆O₅	详情	详情

Extended Information