4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-amine -Drug Synthesis Database

【结构式】

【分子编号】27688

【品名】4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-amine

【CA登记号】

【分子式】C₁₀H₉Cl₂N₃

【分子量】242.10708

【元素组成】C 49.61% H 3.75% Cl 29.29% N 17.36%

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：(I)

The cyclization of 5-aminopyrazole (I) with ethyl acetoacetate (II) by means of p-tolulenesulfonic acid in refluxing toluene gives the pyrazolo-pyrimidinone (III), along with its undesired isomer that is separated by crystallization or chromatography. The reaction of (III) with POCl3 gives the chloro derivative (IV), which is finally condensed with butylethylamine (V).

参考文献中间体

合成目标

【1】 Nakada, N.; et al.; Mechanism of inhibition of DNA gyrase by cyclothialidine, a novel DNA gyrase inhibitor. Antimicrob Agents Chemother 1994, 38, 9, 1966.

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)	27688	4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-amine		C₁₀H₉Cl₂N₃	详情	详情
(II)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(III)	27689	3-(2,4-dichlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-7(4H)-one		C₁₄H₁₁Cl₂N₃O	详情	详情
(IV)	27690	7-chloro-3-(2,4-dichlorophenyl)-2,5-dimethylpyrazolo[1,5-a]pyrimidine		C₁₄H₁₀Cl₃N₃	详情	详情
(V)	26788	N-butyl-N-ethylamine	13360-63-9	C₆H₁₅N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Claisen condensation of 2,4-dichlorophenylacetonitrile (I) with ethyl acetate using of Na metal gave ketonitrile (II), which was reacted with hydrazine hydrate in the presence of AcOH to afford aminopyrazole (III). Subsequent condensation of (III) with ethyl acetimidate (IV) produced amidine (V). This was cyclized with diethyl carbonate and NaOEt to furnish the pyrazolotriazinone (VI). Chlorination of (VI) using phosphoryl chloride in N,N-dimethylaniline provided chloride (VII), which was finally coupled with 1,3-dimethoxy-2-aminopropane (VIII) to yield the title compound.

参考文献中间体

合成目标

【1】 Gilligan, P.J.; He, L.; Zaczek, R.; et al.; 4-(1,3-Dimethoxyprop-2-ylamino)-2,7-dimethyl-8-(2,4-dichlorophenyl)pyrazolo[1,5-a]-1,3,5-triazine: A potent, orally bioavailable CRF1 receptor antagonist. J Med Chem 2000, 43, 3, 449.
【2】 Arvanitis, A.G.; Chorvat, R.J. (DuPont Pharmaceuticals Co.); Azolo triazines and pyrimidines. US 6124289; WO 9803510 .

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)	28484	2,4.Dichlorobenzyl cyanide; 2-(2,4-Dichlorophenyl)acetonitrile	6306-60-1	C₈H₅Cl₂N	详情	详情
(II)	28485	2-(2,4-dichlorophenyl)-3-oxobutanenitrile		C₁₀H₇Cl₂NO	详情	详情
(III)	27688	4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-amine		C₁₀H₉Cl₂N₃	详情	详情
(IV)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(V)	28486	N-[4-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5-yl]ethanimidamide		C₁₂H₁₂Cl₂N₄	详情	详情
(VI)	28487	8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazin-4(3H)-one		C₁₃H₁₀Cl₂N₄O	详情	详情
(VII)	28488	4-chloro-8-(2,4-dichlorophenyl)-2,7-dimethylpyrazolo[1,5-a][1,3,5]triazine		C₁₃H₉Cl₃N₄	详情	详情
(VIII)	23336	1,3-dimethoxy-2-propanamine		C₅H₁₃NO₂	详情	详情

Extended Information