4-Chloro-3-nitroquinoline -Drug Synthesis Database

【结构式】

【分子编号】11664

【品名】4-Chloro-3-nitroquinoline

【CA登记号】

【分子式】C₉H₅ClN₂O₂

【分子量】208.60368

【元素组成】C 51.82% H 2.42% Cl 17% N 13.43% O 15.34%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

The condensation of 4-chloro-3-nitroquinoline (I) with isobutylamine in refluxing THF gives 4-(isobutylamino)-3-nitroquinoline (II), which by reduction with H2 over Pt/C in ethanol is converted to 3-amino-4-(isobutylamino)quinoline (III). The cyclization of (III) with triethyl orthoformate in refluxing formic acid affords 1-isobutyl-1H-imidazo[4,5-c]quinoline (IV), which is oxidized with 30% H2O2 in hot acetic acid yielding 1-isobutyl-1H-imidazo[4,5-c]quinolin-5-oxide (V). The reaction of (V) with refluxing POCl3 affords 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (VI), which is finally treated with concentrated aqueous NH4OH at 150 C in a pressure vessel.

参考文献中间体

合成目标

【1】 Gerster, J.F. (3M Pharmaceuticals); 1H-Imidazo[4,5-c]quinolines and 1H-imidazo[4, 5-c]quinolin-4-amines. EP 0145340; US 4689338; US 4698348 .
【2】 Prous, J.; Castaner, J.; S-26308. Drugs Fut 1989, 14, 9, 870.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	11664	4-Chloro-3-nitroquinoline	C₉H₅ClN₂O₂	详情	详情
(II)	21313	N-isobutyl-3-nitro-4-quinolinamine	C₁₃H₁₅N₃O₂	详情	详情
(III)	21314	N-(3-amino-4-quinolinyl)-N-isobutylamine	C₁₃H₁₇N₃	详情	详情
(IV)	21315	1-isobutyl-1H-imidazo[4,5-c]quinoline	C₁₄H₁₅N₃	详情	详情
(V)	21316	1-isobutyl-1H-imidazo[4,5-c]quinolin-5-ium hydroxide	C₁₄H₁₇N₃O	详情	详情
(VI)	21317	4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline	C₁₄H₁₄ClN₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Nitroacetaldehyde oxime (I) is formed from nitromethane in the presence of NaOH and is converted in acidic media with 2-aminobenzoic acid (II) to 2-(2-nitroethylideneamino)benzoic acid (III). Cyclization of (III) in acetic anhydride by means of potassium acetate yields 4-hydroxy-3-nitroquinoline (IV), which is converted to 4-chloro-3-nitroquinoline (V) in boiling POCl3. Reaction of (V) with morpholinecarboximidamide (VIII) (formed from morpholine (VI) and S-methylisothiourea hemisulfate (VII) in ethanol) affords troquidazole.

参考文献中间体

合成目标

【1】 Berényi, E.; Varga, L.; Pallos, L.; Petöcz, L.; Ladányi, L.; Tömpe, P.; Hartai, E.; Kovács, A. (Egis Pharmaceuticals Ltd.); N-(3-Nitroquinolin-4-yl)guanidine derivatives as radiosensitizers. (EGIS Pharm., Ltd.). BE 0904864; CH 668069; ES 8707231; GB 2176185; JP 1987048668; US 4652562 .
【2】 Nógrádi, M.; Berényi, E.; Blaskó, G.; Troquidazole. Drugs Fut 1992, 17, 5, 384.

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)	11660	2-Nitroacetaldehyde oximesodium salt		C₂H₃N₂NaO₃	详情	详情
(II)	11661	2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid	118-92-3	C₇H₇NO₂	详情	详情
(III)	11662	2-[[(E)-2-Nitroethylidene]amino]benzoic acid		C₉H₈N₂O₄	详情	详情
(IV)	11663	3-Nitro-4-quinolinol; 3-Nitro-quinolin-4-ol		C₉H₆N₂O₃	详情	详情
(V)	11664	4-Chloro-3-nitroquinoline		C₉H₅ClN₂O₂	详情	详情
(VI)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(VII)	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情
(VIII)	11667	4-Morpholinecarboximidamide		C₅H₁₁N₃O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XI)

The condensation of the chiral oxazolidinone (I) with the pentenoic anhydride (II) by means of n-BuLi in THF gives the N-pentenoyloxazolidinone (III), which is condensed with acrolein (IV) catalyzed by TiCl4 and (-)-spartein in dichloromethane, yielding the chiral adduct (V). The ring-closing metathesis of (V) by means of a Ru catalyst in dichloromethane affords the chiral cyclopentenol derivative (VI), which is reduced to the (R,R)-5-(hydroxymethyl)-2-cyclopenten-1-ol (VII) by means of LiBH4 in THF. The reaction of diol (VII) with Ac2O; with methyl chloroformate, TEA and DMAP; or with ethyl chloroformate and pyridine gives the diacetate (VIII), the cyclic carbonate (IX) or the dicarbonate (X), respectively. The condensation of (VIII), (IX) or (X) with 2-amino-6-chloropurine (XI) by means of Pd(PPh3)4 yields the carbocyclic purines (XII), (XIII) or (XIV), respectively. Finally, these compounds are hydrolyzed with aqueous NaOH to the target carbocyclic guanine.

参考文献中间体

合成目标

【1】 Crimmins, M.T.; et al.; An efficient, general asymmetric synthesis of carbocyclic nucleosides: Application of an asymmetric aldol/ring-closing metathesis strategy. J Org Chem 2000, 65, 25, 8499.

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)	14694	(S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone	90719-32-7	C₁₀H₁₁NO₂	详情	详情
(II)	17666	1,1-dimethylpropionic 4-pentenoic anhydride		C₁₀H₁₆O₃	详情	详情
(III)	17667	(4S)-4-benzyl-3-(4-pentenoyl)-1,3-oxazolidin-2-one		C₁₅H₁₇NO₃	详情	详情
(IV)	17668	acrylaldehyde; Acrolein	107-02-8	C₃H₄O	详情	详情
(V)	17669	(4S)-3-[(2S,3R)-2-allyl-3-hydroxy-4-pentenoyl]-4-benzyl-1,3-oxazolidin-2-one		C₁₈H₂₁NO₄	详情	详情
(VI)	17670	(4S)-4-benzyl-3-[[(1S,2R)-2-hydroxy-3-cyclopenten-1-yl]carbonyl]-1,3-oxazolidin-2-one		C₁₆H₁₇NO₄	详情	详情
(VII)	17671	(1R,5R)-5-(hydroxymethyl)-2-cyclopenten-1-ol		C₆H₁₀O₂	详情	详情
(VIII)	17674	[(1R,2R)-2-(acetoxy)-3-cyclopenten-1-yl]methyl acetate		C₁₀H₁₄O₄	详情	详情
(IX)	17673	(4aR,7aR)-4,4a,5,7a-tetrahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₈O₃	详情	详情
(X)	17672	[(1R,2R)-2-[(methoxycarbonyl)oxy]-3-cyclopenten-1-yl]methyl methyl carbonate		C₁₀H₁₄O₆	详情	详情
(XI)	11664	4-Chloro-3-nitroquinoline		C₉H₅ClN₂O₂	详情	详情
(XII)	45424	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl acetate		C₁₃H₁₄ClN₅O₂	详情	详情
(XIII)	17650	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情
(XIV)	45398	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl methyl carbonate		C₁₃H₁₄ClN₅O₃	详情	详情

Extended Information