ethyl (E)-3-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]-2-propenoate -Drug Synthesis Database

【结构式】

【分子编号】40649

【品名】ethyl (E)-3-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]-2-propenoate

【CA登记号】

【分子式】C₁₈H₂₂N₄O₄

【分子量】358.39724

【元素组成】C 60.32% H 6.19% N 15.63% O 17.86%

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：(VIII)

Methylation of 5-iodovanillin (I) with dimethyl sulfate and K2CO3 afforded dimethoxy derivative (II). This was condensed with 3-anilinopropionitrile (III) in the presence of potassium tert-butoxide yielding the enamino nitrile (IV). Subsequent cyclization of (IV) with guanidine hydrochloride (V) produced diaminopyrimidine (VI). Cinnamate derivative (VIII) was then obtained by palladium-catalyzed coupling of (VI) with ethyl acrylate (VII).

参考文献中间体

合成目标

【1】 Guerry, P.; Locher, H.H.; Hubschwerlen, C.; Wyss, P.C.; Jolidon, S.; Hartman, P.G.; Stalder, H.; Specklin, J.L.; Anti-MRSA dihydrofolate reductase inhibitors: Synthesis and SAR. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F1800.

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)	12758	4-Hydroxy-3-iodo-5-methoxybenzaldehyde; 5-Iodovanillin	5438-36-8	C₈H₇IO₃	详情	详情
(II)	40641	3-iodo-4,5-dimethoxybenzaldehyde	32024-15-0	C₉H₉IO₃	详情	详情
(III)	27195	3-anilinopropanenitrile	1075-76-9	C₉H₁₀N₂	详情	详情
(IV)	40642	(Z)-3-anilino-2-(3-iodo-4,5-dimethoxybenzyl)-2-propenenitrile		C₁₈H₁₇IN₂O₂	详情	详情
(V)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情
(VI)	40643	5-(3-iodo-4,5-dimethoxybenzyl)-2,4-pyrimidinediamine; 2-amino-5-(3-iodo-4,5-dimethoxybenzyl)-4-pyrimidinylamine		C₁₃H₁₅IN₄O₂	详情	详情
(VII)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(VIII)	40649	ethyl (E)-3-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]-2-propenoate		C₁₈H₂₂N₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Lithiopyrimidine (X), prepared from 5-bromo-2-methylpyrimidine (IX) was added to phthalazine (XI) to produce adduct (XII). Displacement of ester (VIII) by dihydrophthalazine (XII) in the presence of butyllithium furnished the corresponding racemic amide. The desired (R)-enantiomer was finally isolated by chiral chromatography on a Chiralpak AD column.

参考文献中间体

合成目标

【1】 Guerry, P.; Locher, H.H.; Hubschwerlen, C.; Wyss, P.C.; Jolidon, S.; Hartman, P.G.; Stalder, H.; Specklin, J.L.; Anti-MRSA dihydrofolate reductase inhibitors: Synthesis and SAR. 39th Intersci Conf Antimicrob Agents Chemother (Sept 26 1999, San Francisco) 1999, Abst F1800.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	40650	5-bromo-2-methylpyrimidine		C₅H₅BrN₂	详情	详情
(X)	40651	(2-methyl-5-pyrimidinyl)lithium		C₅H₅LiN₂	详情	详情
(XI)	40652	phthalazine	253-52-1	C₈H₆N₂	详情	详情
(XII)	40653	1-(2-methyl-5-pyrimidinyl)-1,2-dihydrophthalazine		C₁₃H₁₂N₄	详情	详情
(XIII)	40649	ethyl (E)-3-[5-[(2,4-diamino-5-pyrimidinyl)methyl]-2,3-dimethoxyphenyl]-2-propenoate		C₁₈H₂₂N₄O₄	详情	详情

Extended Information