3,5-dibromo-2-pyrazinamine -Drug Synthesis Database

【结构式】

【分子编号】26178

【品名】3,5-dibromo-2-pyrazinamine

【CA登记号】24241-18-7

【分子式】C₄H₃Br₂N₃

【分子量】252.89604

【元素组成】C 19% H 1.2% Br 63.19% N 16.62%

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 precursor imidazopyrazine (III) was prepared by condensation of 2-amino-3,5-dibromopyrazine (I) with ethyl 3-bromopyruvate (II). Subsequent treatment of ester (III) with aqueous ammonia produced the corresponding amide (IV). This was then dehydrated with phosphoryl chloride, with concomitant displacement of the 8-bromine for a chloro group, to yield nitrile (V). Finally, substitution of the chloride by methyl amine in (V) furnished the target compound.

参考文献中间体

合成目标

【1】 Sablayrolles, C.; et al.; Synthesis of imidazo[1,2-a]pyrazine derivatives with uterine-relaxing, antibronchospastic, and cardiac-stimulating properties. J Med Chem 1984, 27, 2, 206.
【2】 Vitse, O.; Laurent, F.; Pocock, T.M.; et al.; New imidazol[1,2-a]pyrazine derivatives withbronchodilatory and cyclic nucleotide phosphodiesterase inhibitory activities. Bioorg Med Chem 1999, 7, 6, 1059.

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)	26178	3,5-dibromo-2-pyrazinamine	24241-18-7	C₄H₃Br₂N₃	详情	详情
(II)	25183	ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate	70-23-5	C₅H₇BrO₃	详情	详情
(III)	26179	ethyl 6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxylate		C₉H₇Br₂N₃O₂	详情	详情
(IV)	26180	6,8-dibromoimidazo[1,2-a]pyrazine-2-carboxamide		C₇H₄Br₂N₄O	详情	详情
(V)	26181	6-bromo-8-chloroimidazo[1,2-a]pyrazine-2-carbonitrile		C₇H₂BrClN₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of 2-amino-3,5-dibromopyrazine (I) with neat 3-amino-pentane (II) under microwave irradiation at 150 °C yields the diaminopyrazine (III), which is then subjected to cyclization with CDI in refluxing THF to give 6-bromo-1-(3-pentyl)imidazo[4,5-b]pyrazin-2-ol (IV). Sonogashira cross-coupling of aryl bromide (IV) with (trimethylsilyl)acetylene (V) in the presence of PdCl2(PPh3)2, CuI and Et3N in DMF at 80 °C affords adduct (VI), which is finally desilylated by treatment with KF in MeOH/THF/H2O .

参考文献中间体

合成目标

【1】 Muci, A., Finer, J.T., Lu, P.-P., Russell, A.J., Morgan, B.P., Morgans, D.J. Jr. (Cytokinetics, Inc.). Certain chemical entities, compositions and methods. EP 2069352, JP 2009545596, US 2008146561, US 7598248, US 8227603, US 8299248, WO 200801669.

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)	26178	3,5-dibromo-2-pyrazinamine	24241-18-7	C₄H₃Br₂N₃	详情	详情
(II)	25924	1-ethylpropylamine; 3-pentanamine	616-24-0	C₅H₁₃N	详情	详情
(III)	67991	6-bromo-N²-(pentan-3-yl)pyrazine-2,3-diamine		C₉H₁₅BrN₄	详情	详情
(IV)	67992	6-bromo-1-(3-pentyl)imidazo[4,5-b]pyrazin-2-ol		C₁₀H₁₃BrN₄O	详情	详情
(V)	23897	ethynyl(trimethyl)silane；trimethylsilyl acetylene	1066-54-2	C₅H₁₀Si	详情	详情
(VI)	67993	1-(pentan-3-yl)-6-((trimethylsilyl)ethynyl)-1H-imidazo[4,5-b]pyrazin-2-ol		C₁₅H₂₂N₄OSi	详情	详情

Extended Information