4,6-Dichloro-2-(methylsulfonyl)pyrimidine; 2-(Methylsulfonyl)-4,6-Dichloropyrimidine; NSC 45040 -Drug Synthesis Database

【结构式】

【分子编号】65247

【品名】4,6-Dichloro-2-(methylsulfonyl)pyrimidine; 2-(Methylsulfonyl)-4,6-Dichloropyrimidine; NSC 45040

【CA登记号】4489-34-3

【分子式】C₅H₄Cl₂N₂O₂S

【分子量】227.07044

【元素组成】C 26.45% H 1.78% Cl 31.23% N 12.34% O 14.09% S 14.12%

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：(II)

The oxidation of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (I) with MCPBA in dichloromethane gives 4,6-dichloro-2-(methylsulfonyl)pyrimidine (II), which is condensed with N-(4-sulfanylphenyl)cyclopropanecarboxamide (III) in hot butanol to yield the diaryl thioether (IV). The reaction of (IV) with 3-methyl-1H-pyrazol-5-amine (V) by means of DIEA in hot DMF affords the secondary amine (VI), which is finally condensed with 1-methylpiperazine (VII) by heating at 110 ºC to provide the target compound (1). Scheme 1.

参考文献中间体

合成目标

【1】 Charrier, J.-D., Kay, D., Mazzei, F., Miller, A. (Vertex Pharmaceuticals, Inc.). Processes for preparing substd. pyrimidines and pyrimidine derivs. as inhibitors of protein kinase. EP 1517905, EP 1746093, JP 2005320351, JP 2006501176, US 2004049032, WO 2004000833.

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)	65246	4,6-Dichloro-2-(methylthio)pyrimidine；4,6-dichloro-2-(methylsulfanyl)pyrimidine	6299-25-8	C₅H₄Cl₂N₂S	详情	详情
(II)	65247	4,6-Dichloro-2-(methylsulfonyl)pyrimidine; 2-(Methylsulfonyl)-4,6-Dichloropyrimidine; NSC 45040	4489-34-3	C₅H₄Cl₂N₂O₂S	详情	详情
(III)	65248	N-(4-mercaptophenyl)cyclopropanecarboxamide	639090-54-3	C₁₀H₁₁NOS	详情	详情
(IV)	65249			C₁₃H₁₁Cl₂N₃OS	详情	详情
(V)	65250	5-amino-3-methyl-1H-pyrazole		C₄H₇N₃	详情	详情
(VI)	65251			C₁₇H₁₇ClN₆OS	详情	详情
(VII)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Oxidation of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (I) with 3-chlorobenzoyl peroxide in CH2Cl2 gives the sulfonyl derivative (II), which is alkynylated with phenylacetylenyl magnesium bromide (III) in THF to provide 4,6-dichloro-2-(phenylethynyl)pyrimidine (IV). Condensation of the dichloropyrimidine derivative (IV) with 5-methyl-3-aminopyrazole (V) by means of NaI and DIEA in DMA at 90 °C affords amine (VI), which is coupled with N-methylpiperazine (VII) in the presence of DMAP and DIEA in 1,4-dioxane at 100 °C to furnish the piperazinyl derivative (VIII). Reduction of alkyne (VIII) by means of LiAlH4 in THF gives alkene (IX), which is finally treated with sodium potassium tartrate .

参考文献中间体

合成目标

【1】 Xiao, X.-Y., Patel, D.V., Ward, J.S., Bray, M.R., Agoston, G.E., Treston, A.M.(Miikana Therapeutics, Inc.). Substituted pyrazole compounds. EP 1928456, JP 2009510107, US 2007142368, WO 2007041358.

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)	65246	4,6-Dichloro-2-(methylthio)pyrimidine；4,6-dichloro-2-(methylsulfanyl)pyrimidine	6299-25-8	C₅H₄Cl₂N₂S	详情	详情
(II)	65247	4,6-Dichloro-2-(methylsulfonyl)pyrimidine; 2-(Methylsulfonyl)-4,6-Dichloropyrimidine; NSC 45040	4489-34-3	C₅H₄Cl₂N₂O₂S	详情	详情
(III)	32758	bromo(2-phenylethynyl)magnesium；phenylacetylenyl magnesium bromide;(phenylethynyl)magnesium bromide		C₈H₅BrMg	详情	详情
(IV)	68677	4,6-dichloro-2-(phenylethynyl)pyrimidine		C₁₂H₆Cl₂N₂	详情	详情
(V)	68679	5-methyl-3-aminopyrazole;3-Amino-5-methylpyrazole;3-Methyl-1H-pyrazol-5-amine	31230-17-8	C₄H₇N₃	详情	详情
(VI)	68678	6-chloro-N-(5-methyl-1H-pyrazol-3-yl)-2-(phenylethynyl)pyrimidin-4-amine		C₁₆H₁₂ClN₅	详情	详情
(VII)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(VIII)	68680	N-(5-methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-(phenylethynyl)pyrimidin-4-amine		C₂₁H₂₃N₇	详情	详情
(IX)	68681	N-(5-methyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-styrylpyrimidin-4-amine;6-(4-Methyl-1-piperazinyl)-N-(5-methyl-1H-pyrazol-3-yl)-2-[(1E)-2-phenylethenyl]-4-pyrimidinamine	934353-76-1	C₂₁H₂₅N₇	详情	详情

Extended Information