NS-8, -Drug Synthesis Database

【结构式】

【药物名称】NS-8

【化学名称】2-Amino-5-(2-fluorophenyl)-4-methyl-1H-pyrrole-3-carbonitrile

【CA登记号】186033-14-7

【分子式】C₁₂H₁₀FN₃

【分子量】215.232

【开发单位】Nippon Shinyaku (Originator), Apogepha (Licensee)

【药理作用】RENAL-UROLOGIC DRUGS, Urinary Incontinence Therapy, Large Conductance BK(Ca) Channel Activators

合成路线1 合成路线2

合成路线1

Treatment of 2-fluorophenylglycine (I) with Ac2O and pyridine at 150 C produced 1-(2-fluorophenyl)-1-acetamido-2-propanone (II). This was subsequently condensed with malononitrile yielding the title pyrrole derivative.

参考文献中间体

【1】 Tsuda, M.; Tanaka, M.; Nakamura, A. (Nippon Shinyaku Co., Ltd.); Pyrrole derivs. and medicinal compsn.. US 5998459; WO 9640634 .

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)	41116	2-amino-2-(2-fluorophenyl)acetic acid	84145-28-8	C₈H₈FNO₂	详情	详情
(II)	41117	N-[1-(2-fluorophenyl)-2-oxopropyl]acetamide		C₁₁H₁₂FNO₂	详情	详情

合成路线2

The partial hydrolysis of malonodinitrile (I) with HCl in ethanol gives 2-cyanoacetamide (II), which is treated with ammonia in ethanol to yield 3,3-diaminopropenenitrile (III). Finally, this compound is cyclized with 2-bromo-1-(2-fluorophenyl)-1-propanone (IV) by means of TEA in ethanol.

参考文献中间体

【1】 Tsuda, M.; et al.; Studies on potassium channel openers: Synthesis and pharmacological properties of novel pyrrole derivatives. 20th Symp Med Chem (Dec 6 2000, Tokyo) 2000, Abst 2P-24.

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)	12061	Malononitrile	109-77-3	C₃H₂N₂	详情	详情
(II)	12122	Cyanoacetamide; 2-Cyanoacetamide	107-91-5	C₃H₄N₂O	详情	详情
(III)	42081	3,3-diaminoacrylonitrile		C₃H₅N₃	详情	详情
(IV)	42082	2-bromo-1-(2-fluorophenyl)-1-propanone		C₉H₈BrFO	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)