[4-amino-3-(isopropylamino)phenyl](2,3-difluorophenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】37891

【品名】[4-amino-3-(isopropylamino)phenyl](2,3-difluorophenyl)methanone

【CA登记号】

【分子式】C₁₆H₁₆F₂N₂O

【分子量】290.3127264

【元素组成】C 66.2% H 5.56% F 13.09% N 9.65% O 5.51%

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：(VI)

Treatment of 2,4-difluoronitrobenzene (I) with isopropylamine in the presence of K2CO3 in THF afforded 2-isopropylamino-4-fluoronitrobenzene (II). Subsequent condensation of (II) with 2,3-difluorophenylacetonitrile (III) by means of potassium tert-butoxide, followed by oxidative treatment of the intermediate nitrile (IV) with H2O2 generated benzophenone (V). The nitro group of (V) was then reduced by hydrogenation over Raney Nickel yielding diamine (VI), which was cyclized to benzimidazole (VII) upon treatment with cyanogen bromide. Addition of the lithium anion of N-methyl-N-(trimethylsilyl)acetamide to (VII) gave beta-hydroxyamide (VIII). Finally, acid promoted dehydration of (VIII) furnished the corresponding alpha,beta-unsaturated amide.

参考文献中间体

合成目标

【1】 Jungheim, L.N.; Shepherd, T.A.; Spitzer, W.A.; Tebbe, M.J. (Eli Lilly and Company); Anti-viral cpds.. EP 0906097; WO 9746237 .

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)	32036	2,4-difluoro-1-nitrobenzene	446-35-5	C₆H₃F₂NO₂	详情	详情
(II)	37887	5-fluoro-N-isopropyl-2-nitroaniline; N-(5-fluoro-2-nitrophenyl)-N-isopropylamine		C₉H₁₁FN₂O₂	详情	详情
(III)	37888	2-(2,3-difluorophenyl)acetonitrile	145689-34-5	C₈H₅F₂N	详情	详情
(IV)	37889	2-(2,3-difluorophenyl)-2-[3-(isopropylamino)-4-nitrophenyl]acetonitrile		C₁₇H₁₅F₂N₃O₂	详情	详情
(V)	37890	(2,3-difluorophenyl)[3-(isopropylamino)-4-nitrophenyl]methanone		C₁₆H₁₄F₂N₂O₃	详情	详情
(VI)	37891	[4-amino-3-(isopropylamino)phenyl](2,3-difluorophenyl)methanone		C₁₆H₁₆F₂N₂O	详情	详情
(VII)	37892	(2-amino-1-isopropyl-1H-benzimidazol-6-yl)(2,3-difluorophenyl)methanone		C₁₇H₁₅F₂N₃O	详情	详情
(VIII)	37894	3-(2-amino-1-isopropyl-1H-benzimidazol-6-yl)-3-(2,3-difluorophenyl)-3-hydroxy-N-methylpropanamide		C₂₀H₂₂F₂N₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Treatment of 2,4-difluoronitrobenzene (I) with isopropylamine in the presence of K2CO3 in THF afforded 2-isopropylamino-4-fluoronitrobenzene (II). Subsequent condensation of (II) with 2,3-difluorophenylacetonitrile (III) by means of potassium tert-butoxide, followed by oxidative treatment of the intermediate nitrile (IV) with H2O2 generated benzophenone (V). The nitro group of (V) was then reduced by hydrogenation over Raney Nickel yielding diamine (VI), which was cyclized to benzimidazole (VII) upon treatment with cyanogen bromide. Addition of the lithium anion of bis(trimethylsilyl)acetamide to (VII) gave beta-hydroxyamide (VIII). Finally, acid promoted dehydration of (VIII) furnished the corresponding alpha,beta-unsaturated amide, which was isoalted as the hydrochloride salt.

参考文献中间体

合成目标

【1】 Jungheim, L.N.; Shepherd, T.A.; Spitzer, W.A.; Tebbe, M.J. (Eli Lilly and Company); Anti-viral cpds.. EP 0906097; WO 9746237 .

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)	32036	2,4-difluoro-1-nitrobenzene	446-35-5	C₆H₃F₂NO₂	详情	详情
(II)	37887	5-fluoro-N-isopropyl-2-nitroaniline; N-(5-fluoro-2-nitrophenyl)-N-isopropylamine		C₉H₁₁FN₂O₂	详情	详情
(III)	37888	2-(2,3-difluorophenyl)acetonitrile	145689-34-5	C₈H₅F₂N	详情	详情
(IV)	37889	2-(2,3-difluorophenyl)-2-[3-(isopropylamino)-4-nitrophenyl]acetonitrile		C₁₇H₁₅F₂N₃O₂	详情	详情
(V)	37890	(2,3-difluorophenyl)[3-(isopropylamino)-4-nitrophenyl]methanone		C₁₆H₁₄F₂N₂O₃	详情	详情
(VI)	37891	[4-amino-3-(isopropylamino)phenyl](2,3-difluorophenyl)methanone		C₁₆H₁₆F₂N₂O	详情	详情
(VII)	37892	(2-amino-1-isopropyl-1H-benzimidazol-6-yl)(2,3-difluorophenyl)methanone		C₁₇H₁₅F₂N₃O	详情	详情
(VIII)	37893	3-(2-amino-1-isopropyl-1H-benzimidazol-6-yl)-3-(2,3-difluorophenyl)-3-hydroxypropanamide		C₁₉H₂₀F₂N₄O₂	详情	详情

Extended Information