4-chloro-3-nitropyridine -Drug Synthesis Database

【结构式】

【分子编号】29971

【品名】4-chloro-3-nitropyridine

【CA登记号】

【分子式】C₅H₃ClN₂O₂

【分子量】158.5438

【元素组成】C 37.88% H 1.91% Cl 22.36% N 17.67% O 20.18%

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：(IX)

The acetylation of 2-methyl-3-aminobenzonitrile (I) with acetic anhydride in refluxing acetic acid gives 2-methyl-3-acetylaminobenzonitrile (II), which is reduced with Raney-Ni in refluxing 50% formic acid yielding 2-methyl-3-acetylaminobenzaldehyde (III). The condensation of (III) with malonic acid (IV) by means of piperidine in pyridine affords 2-methyl-3-acetylaminocinn acid (V), which is converted to the corresponding azide (VI) by reaction with ethyl chloroformate and sodium azide by means of triethylamine in acetone. The cyclization of (VI) by heating at 240 C in diphenyl ether gives 1-hydroxy-5-methyl-6-acetylaminoisoquinoline (VII), which is hydrolyzed with HCl in refluxing ethanol to 1-hydroxy-5-methyl-6-aminoisoquinoline (VIII). The condensation of (VIII) with 4-chloro-3-nitropyridine (IX) in DMF affords 1-hydroxy-5-methyl-6-[(3-nitro-4-pyridyl)amino]isoquinoline (X).

参考文献中间体

合成目标

【1】 Rivalle, C.; Lhoste, J.M.; Bisagni, E.; Duerocq, C.; Synthesis of 10-substituted 5H-pyrido[3',4':4,5]pyrrolo[2,3-g]isoquinolines. J Chem Soc - Perkins Trans I 1979, 142-145.
【2】 Van der Burg, W.J. (Akzo Nobel N.V.); Tetracyclic compounds. BE 0840362; CH 622261; DE 2614406; DK 142498; ES 446634; FR 2305986; GB 1543171; JP 76122099; NL 754075 .
【3】 Hopkins, S.J.; Serradell, M.N.; Castaner, J.; BD-40. Drugs Fut 1984, 9, 2, 96.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	29968	N-(5-methyl-1-oxo-1,2-dihydro-6-isoquinolinyl)acetamide		C₁₂H₁₂N₂O₂	详情	详情
(I)	29963	3-amino-2-methylbenzonitrile		C₈H₈N₂	详情	详情
(II)	29964	N-(3-cyano-2-methylphenyl)acetamide		C₁₀H₁₀N₂O	详情	详情
(III)	29965	N-(3-formyl-2-methylphenyl)acetamide		C₁₀H₁₁NO₂	详情	详情
(IV)	12963	Malonic acid	141-82-2	C₃H₄O₄	详情	详情
(V)	29966	(Z)-3-[3-(acetamido)-2-methylphenyl]-2-propenoic acid		C₁₂H₁₃NO₃	详情	详情
(VI)	29967	(Z)-3-[3-(acetamido)-2-methylphenyl]-2-propenoyl azide		C₁₂H₁₂N₄O₂	详情	详情
(VII)	29969	N-(1-hydroxy-5-methyl-6-isoquinolinyl)acetamide		C₁₂H₁₂N₂O₂	详情	详情
(VIII)	29970	6-amino-5-methyl-1-isoquinolinol		C₁₀H₁₀N₂O	详情	详情
(IX)	29971	4-chloro-3-nitropyridine		C₅H₃ClN₂O₂	详情	详情
(X)	29972	5-methyl-6-[(3-nitro-4-pyridinyl)amino]-1-isoquinolinol		C₁₅H₁₂N₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

4-(Aminomethyl)piperidine (I) was selectively protected at the piperidine N by means of Boc2O. The resultant 1-Boc-4-(aminomethyl)piperidine (II) was condensed with 4-chloro-3-nitropyridine (III) to afford the amino pyridine compound (IV). Catalytic hydrogenation of the nitro group of (IV) furnished the 3,4-diaminopyridine (V), which was cyclized with ethyl acetimidate hydrochloride (VI) to produce the imidazopyridine (VII). Subsequent acid cleavage of the Boc protecting group of (VII) provided the intermediate piperidine (VIII).

参考文献中间体

合成目标

【1】 Carceller, E.; Jimenez, P.J.; Salas, J.; Almansa, C.; Bartroli, J.; Merlos, M.; Giral, M.; Balsa, D.; Ferrando, R.; Garcia-Rafanell, J.; Forn, J. (J. Uriach & Cía., SA); Azo derivs. of 5-aminosalicylic acid for treatment of inflammatory bowel disease. EP 0790998; ES 2104513; ES 2106682; JP 1999501939; US 5747477; WO 9709329 .

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)	19349	4-piperidinylmethylamine; 4-piperidinylmethanamine; 4-(Aminomethyl)piperidine	7144-05-0	C₆H₁₄N₂	详情	详情
(II)	19352	4-Aminomethyl-1-N-Boc-piperidine; tert-butyl 4-(aminomethyl)-1-piperidinecarboxylate	144222-22-0	C₁₁H₂₂N₂O₂	详情	详情
(III)	29971	4-chloro-3-nitropyridine		C₅H₃ClN₂O₂	详情	详情
(IV)	59460	tert-butyl 4-{[(3-nitro-4-pyridinyl)amino]methyl}-1-piperidinecarboxylate		C₁₆H₂₄N₄O₄	详情	详情
(V)	59461	tert-butyl 4-{[(3-amino-4-pyridinyl)amino]methyl}-1-piperidinecarboxylate		C₁₆H₂₆N₄O₂	详情	详情
(VI)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(VII)	59462	tert-butyl 4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinecarboxylate		C₁₈H₂₆N₄O₂	详情	详情
(VIII)	59463	2-methyl-1-(4-piperidinylmethyl)-1H-imidazo[4,5-c]pyridine		C₁₃H₁₈N₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

4-(Aminomethyl)piperidine (I) was selectively protected at the piperidine N by means of Boc2O. The resultant 1-Boc-4-(aminomethyl)piperidine (II) was condensed with 4-chloro-3-nitropyridine (III) to afford the amino pyridine compound (IV). Catalytic hydrogenation of the nitro group of (IV) furnished the 3,4-diaminopyridine (V), which was cyclized with ethyl acetimidate hydrochloride (VI), to produce the imidazopyridine (VII). Subsequent acid cleavage of the Boc protecting group of (VII) provided the intermediate piperidine (VIII).

参考文献中间体

合成目标

【1】 Carceller, E.; Jimenez, P.J.; Salas, J.; Almansa, C.; Bartroli, J.; Merlos, M.; Giral, M.; Balsa, D.; Ferrando, R.; Garcia-Rafanell, J.; Forn, J. (J. Uriach & Cía., SA); Azo derivs. of 5-aminosalicylic acid for treatment of inflammatory bowel disease. EP 0790998; ES 2104513; ES 2106682; JP 1999501939; US 5747477; WO 9709329 .

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)	19349	4-piperidinylmethylamine; 4-piperidinylmethanamine; 4-(Aminomethyl)piperidine	7144-05-0	C₆H₁₄N₂	详情	详情
(II)	19352	4-Aminomethyl-1-N-Boc-piperidine; tert-butyl 4-(aminomethyl)-1-piperidinecarboxylate	144222-22-0	C₁₁H₂₂N₂O₂	详情	详情
(III)	29971	4-chloro-3-nitropyridine		C₅H₃ClN₂O₂	详情	详情
(IV)	59460	tert-butyl 4-{[(3-nitro-4-pyridinyl)amino]methyl}-1-piperidinecarboxylate		C₁₆H₂₄N₄O₄	详情	详情
(V)	59461	tert-butyl 4-{[(3-amino-4-pyridinyl)amino]methyl}-1-piperidinecarboxylate		C₁₆H₂₆N₄O₂	详情	详情
(VI)	12831	ethyl ethanimidoate	1000-84-6	C₄H₉NO	详情	详情
(VII)	59462	tert-butyl 4-[(2-methyl-1H-imidazo[4,5-c]pyridin-1-yl)methyl]-1-piperidinecarboxylate		C₁₈H₂₆N₄O₂	详情	详情
(VIII)	59463	2-methyl-1-(4-piperidinylmethyl)-1H-imidazo[4,5-c]pyridine		C₁₃H₁₈N₄	详情	详情

Extended Information