4-chloro-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine -Drug Synthesis Database

【结构式】

【分子编号】45880

【品名】4-chloro-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine

【CA登记号】

【分子式】C₁₈H₂₀ClN₃

【分子量】313.82972

【元素组成】C 68.89% H 6.42% Cl 11.3% N 13.39%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VI)

Condensation of 2,4,6-trimethylaniline (I) with malononitrile derivative (II) in isopropanol yields carbonitrile (III), which is then acetylated by means of Ac2O in HOAc to provide acetamide (IV). Cyclization of (IV) is induced by treatment with phosphoric acid to furnish pyrimidinone (V), which is then converted into chloro derivative (VI) in refluxing POCl3 (1). Coupling of (VI) with secondary amine (VII) in DMSO affords compound (VIII), which is finally fluorinated by treatment with tetrabutylammonium fluoride (TBAF) and toluenesulfonyl fluoride (TsF) in refluxing THF.

参考文献中间体

合成目标

【1】 Chen, Y.L. (Pfizer Inc.); Pyrrolopyrimidines as CRF antagonists. EP 0674641; JP 1995509726; WO 9413676 .
【2】 Chrousos, G.P.; Rice, K.C.; Hsin, L.-W.; Gold, P.W.; Webster, E.L.; Contoreggi, C.; Eckelman, W.C.; Synthesis and biological activity of fluoro-substituted pyrrolo[2,3-d]pyrimidines: The development of potential positron emission tomography imaging agents for the corticotropin-releasing hormone type 1 receptor. Bioorg Med Chem Lett 2000, 10, 8, 707.

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)	28804	2,4,6-trimethylaniline	88-05-1	C₉H₁₃N	详情	详情
(II)	45876	2-(2-bromo-1-methylpropylidene)malononitrile		C₇H₇BrN₂	详情	详情
(III)	45877	2-amino-1-mesityl-4,5-dimethyl-1H-pyrrole-3-carbonitrile		C₁₆H₁₉N₃	详情	详情
(IV)	45878	N-(3-cyano-1-mesityl-4,5-dimethyl-1H-pyrrol-2-yl)acetamide		C₁₈H₂₁N₃O	详情	详情
(V)	45879	7-mesityl-2,5,6-trimethyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one		C₁₈H₂₁N₃O	详情	详情
(VI)	45880	4-chloro-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine		C₁₈H₂₀ClN₃	详情	详情
(VII)	45881	4-(propylamino)-1-butanol		C₇H₁₇NO	详情	详情
(VIII)	45882	4-[(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)(propyl)amino]-1-butanol		C₂₅H₃₆N₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The reaction of 4-chloro-1-butanol (I) with allylamine (II) by means of K2CO3 in refluxing THF gives N-allyl-N-(4-hydroxybutyl)amine (III), which is condensed with the pyrrolo[2,3-d]pyrimidine derivative (IV) by heating at 130 C in DMSO to afford the tertiary amine (V). The reaction of (V) with TBAF and Ts-F in THF provides the 4-fluorobutyl derivative (VI). Finally, the hydrogenation of the allylic double bond of (VI) with H2 over Pd/C in ethanol gives the target LWH-154.

参考文献中间体

合成目标

【1】 Gold, P.W.; Contoreggi, C.; Webster, E.L.; Eckelman, W.C.; Rice, K.C.; Hsin, L.-W.; Chrousos, G.P.; Synthesis of [3H] (4-fluorobutyl)propyl[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amine: A potent radioligand for corticotropin-releasing hormone type 1 receptor. J Label Compd Radiopharm 2000, 43, 9, 899.

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)	22336	4-chloro-1-butanol	928-51-8	C₄H₉ClO	详情	详情
(II)	13672	Allylamine; 2-Propen-1-amine	107-11-9	C₃H₇N	详情	详情
(III)	51571	4-(allylamino)-1-butanol		C₇H₁₅NO	详情	详情
(IV)	45880	4-chloro-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine		C₁₈H₂₀ClN₃	详情	详情
(V)	51572	4-[allyl(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-1-butanol		C₂₅H₃₄N₄O	详情	详情
(VI)	51573	N-allyl-N-(4-fluorobutyl)-N-(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine; N-allyl-N-(4-fluorobutyl)-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine		C₂₅H₃₃FN₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Gold, P.W.; Contoreggi, C.; Webster, E.L.; Eckelman, W.C.; Rice, K.C.; Hsin, L.-W.; Chrousos, G.P.; Synthesis of [3H] (4-fluorobutyl)propyl[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amine: A potent radioligand for corticotropin-releasing hormone type 1 receptor. J Label Compd Radiopharm 2000, 43, 9, 899.

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)	22336	4-chloro-1-butanol	928-51-8	C₄H₉ClO	详情	详情
(II)	13672	Allylamine; 2-Propen-1-amine	107-11-9	C₃H₇N	详情	详情
(III)	51571	4-(allylamino)-1-butanol		C₇H₁₅NO	详情	详情
(IV)	45880	4-chloro-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine		C₁₈H₂₀ClN₃	详情	详情
(V)	51572	4-[allyl(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-1-butanol		C₂₅H₃₄N₄O	详情	详情
(VI)	51573	N-allyl-N-(4-fluorobutyl)-N-(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amine; N-allyl-N-(4-fluorobutyl)-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine		C₂₅H₃₃FN₄	详情	详情

Extended Information