Resiquimod, VML-600, R-848, S-28463, -Drug Synthesis Database

【结构式】

【药物名称】Resiquimod, VML-600, R-848, S-28463

【化学名称】1-[4-Amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol
　　　　　　4-Amino-2-(ethoxymethyl)-alpha,alpha-dimethyl-1H-imidazo[4,5-c]quinoline-1-ethanol

【CA登记号】144875-48-9

【分子式】C₁₇H₂₂N₄O₂

【分子量】314.39049

【开发单位】3M Pharmaceuticals (Originator), Lilly (Licensee)

【药理作用】Anti-Hepatitis C Virus Drugs, Anti-Hepatitis Virus Drugs, Anti-Herpes Virus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs, IMMUNOMODULATING AGENTS, Immunomodulators, Interferon Inducers

合成路线1 合成路线2

合成路线1

The esterification of 3-nitroquinoline-2,4-diol (I) with trifluoromethanesulfonic anhydride (II) gives the disulfonate (III), which is condensed with 2-hydroxyisobutylamine (IV) and triethylamine in dichloromethane, yielding the aminoquinoline (V). The reaction of (V) with dibenzylamine by means of triethylamine in refluxing toluene affords the quinolinediamine (VI), which by reduction of its nitro group with NaBH4 provides the quinolinetriamine (VII). The cyclization of (VII) with 2-ethoxyacetyl chloride (VIII) by means of p-toluenesulfonic acid in refluxing acetonitrile gives the protected imidazoquinoline (IX), which is finally deprotected by treatment with Pd/C and formic acid.

参考文献中间体

【1】 Graul, A.; Castañer, J.; S-28463. Drugs Fut 1999, 24, 6, 622.
【2】 Gerster, J.F.; Crooks, S.L.; Lindstrom, K.J. (3M Pharmaceuticals); 1-Substd., 2-substd. 1H-imidazo[4,5-c]quinolin-4-amines. EP 0582581; JP 1994504789; US 5389640; WO 9215582 .

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)	25005	3-nitro-2,4-quinolinediol		C₉H₆N₂O₄	详情	详情
(II)	25006	3,3-dioxo-1,3-bis(trifluoromethyl)-1lambda(6),3lambda(6)-dithioxane-1,1-dione	358-23-6	C₂F₆O₅S₂	详情	详情
(III)	25007	3-nitro-4-[[(trifluoromethyl)sulfonyl]oxy]-2-quinolinyl trifluoromethanesulfonate		C₁₁H₄F₆N₂O₈S₂	详情	详情
(IV)	25008	1-amino-2-methylpropan-2-ol;1-amino-2-methyl-2-propanol;1,1-Dimethylethanolamine;2-Amino-a,a-dimethylethanol;2-Hydroxy-2-methyl-1-propylamine;2-Hydroxyisobutylamine;2-Methyl-2-hydroxypropylamine;3-Amino-2-methyl-2-propanol	2854-16-2	C₄H₁₁NO	详情	详情
(V)	25009	4-[(2-hydroxy-2-methylpropyl)amino]-3-nitro-2-quinolinyl trifluoromethanesulfonate		C₁₄H₁₄F₃N₃O₆S	详情	详情
(VI)	25010	1-[[2-(dibenzylamino)-3-nitro-4-quinolinyl]amino]-2-methyl-2-propanol		C₂₇H₂₈N₄O₃	详情	详情
(VII)	25011	1-[[3-amino-2-(dibenzylamino)-4-quinolinyl]amino]-2-methyl-2-propanol		C₂₇H₃₀N₄O	详情	详情
(VIII)	25012	2-ethoxyacetyl chloride		C₄H₇ClO₂	详情	详情
(IX)	25013	1-[4-(dibenzylamino)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methyl-2-propanol		C₃₁H₃₄N₄O₂	详情	详情

合成路线2

The cyclization of the diaminoquinoline (I) with ethoxyacetic acid (II) by heating at 120 C gives the imidazoquinoline (III), which is oxidized to the 5-N-oxide (IV) by treatment with peracetic acid. Finally, compound (IV) is aminated by means of ammonium hydroxide and p-toluenesulfonyl chloride in dichloromethane.

参考文献中间体

【1】 Graul, A.; Castañer, J.; S-28463. Drugs Fut 1999, 24, 6, 622.
【2】 Nikolaides, N.; Lindstrom, K.J. (3M Pharmaceuticals); Process for preparing quinolone amines. WO 9417043 .

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)	24965	1-[(3-amino-4-quinolinyl)amino]-2-methyl-2-propanol		C₁₃H₁₇N₃O	详情	详情
(II)	24966	2-ethoxyacetic acid	627-03-2	C₄H₈O₃	详情	详情
(III)	24967	1-[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methyl-2-propanol		C₁₇H₂₁N₃O₂	详情	详情
(IV)	24968	2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-5-ium-5-olate		C₁₇H₂₁N₃O₃	详情	详情

Extended Information