4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino]benzonitrile -Drug Synthesis Database

【结构式】

【分子编号】46617

【品名】4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino]benzonitrile

【CA登记号】

【分子式】C₁₁H₅BrCl₂N₄

【分子量】343.99706

【元素组成】C 38.41% H 1.47% Br 23.23% Cl 20.61% N 16.29%

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：(III)

The reaction of 5-bromo-2,4,6-trichloropyrimidine (I) with 4-aminobenzonitrile (II) by means of DIEA in refluxing dioxane gives the diarylamine (III), which is condensed with 4-hydroxy-3,5-dimethylbenzonitrile (IV) by means of NaH in NMP to yield the corresponding adduct (V). Finally, this compound is treated with ammonia in dioxane at 150 C in a pressure vessel.

参考文献中间体

合成目标

【1】 Heeres, J.; De Corte, B.; Kukla, M.J.; Van Aken, K.J.A.; Janssen, P.A.J.; Ludovici, D.W.; De Jonge, M.R.; Kavash, R.W.; Ho, C.Y.; Koymans, L.M.H. (Janssen Pharmaceutica NV); HIV replication inhibiting pyrimidines. EP 1002795; WO 0027825 .

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)	46616	5-bromo-2,4,6-trichloropyrimidine		C₄BrCl₃N₂	详情	详情
(II)	15361	4-Aminobenzonitrile	873-74-5	C₇H₆N₂	详情	详情
(III)	46617	4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino]benzonitrile		C₁₁H₅BrCl₂N₄	详情	详情
(IV)	31141	4-Hydroxy-3,5-dimethylbenzonitrile; 2,6-Dimethyl-4-hydroxybenzonitrile	4198-90-7	C₉H₉NO	详情	详情
(V)	46618	4-[[5-bromo-6-chloro-2-(4-cyanoanilino)-4-pyrimidinyl]oxy]-3,5-dimethylbenzonitrile		C₂₀H₁₃BrClN₅O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The cyclization of 4-guanidinobenzonitrile (I) with diethyl malonate (II) by means of NaOEt in ethanol gives 4-(4,6-dihydroxypyrimidin-2-ylamino)benzonitrile (III), which is treated with POCl3 to yield the corresponding dichloro derivative (IV). The bromination of (IV) with Br2 and NaHCO3 in methanol/water affords 4-(5-bromo-4,6-dichloropyrimidin-2-ylamino)benzonitrile (V), which is condensed with sodium 4-cyano-2,6-dimethylphenolate (VI) and N-methylpyrrolidone in dioxane to provide the chloro precursor (VII). Finally, this compound is treated with ammonia in isopropanol to yield the target dinitrile derivative.

参考文献中间体

合成目标

【1】 Ludovici, D.W.; De Corte, B.L.; Kukla, M.J.; et al.; Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues. Bioorg Med Chem Lett 2001, 11, 17, 2235.

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)	55735	N-(4-cyanophenyl)guanidine		C₈H₈N₄	详情	详情
(II)	16829	Diethyl malonate	105-53-3	C₇H₁₂O₄	详情	详情
(III)	55736	4-[(4,6-dihydroxy-2-pyrimidinyl)amino]benzonitrile		C₁₁H₈N₄O₂	详情	详情
(IV)	55737	4-[(4,6-dichloro-2-pyrimidinyl)amino]benzonitrile		C₁₁H₆Cl₂N₄	详情	详情
(V)	46617	4-[(5-bromo-4,6-dichloro-2-pyrimidinyl)amino]benzonitrile		C₁₁H₅BrCl₂N₄	详情	详情
(VI)	55738	sodium 4-cyano-2,6-dimethylbenzenolate		C₉H₈NNaO	详情	详情
(VII)	55739	ethyl 1-(2-{[(1S)-1-phenylethyl]amino}acetyl)cyclopropanecarboxylate		C₁₆H₂₁NO₃	详情	详情

Extended Information