N(6)-(4-Fluorobenzyl)-3-nitro-2,6-pyridinediamine; N-(6-Amino-5-nitro-2-pyridinyl)-N-(4-fluorobenzyl)amine -Drug Synthesis Database

【结构式】

【分子编号】13576

【品名】N(6)-(4-Fluorobenzyl)-3-nitro-2,6-pyridinediamine; N-(6-Amino-5-nitro-2-pyridinyl)-N-(4-fluorobenzyl)amine

【CA登记号】

【分子式】C₁₂H₁₁FN₄O₂

【分子量】262.2435032

【元素组成】C 54.96% H 4.23% F 7.24% N 21.36% O 12.2%

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：(IV)

The reaction of 2,6-dichloro-3-nitropyridine (I) with ammonia yields 2-amino-3-nitro-chloropyridine (II). 4-Fluorobenzylamine (III) reacts in dioxane and in the presence of triethylamine with (II), resulting in the 2-amino-3-nitro-6-p-fluorobenzylamine derivative (IV). The latter is hydrated and in situ the 3-amino group is condensed with ethyl chloroformate leading to the stable 2-amino-3-carbethoxyamino-6-(p-fluorobenzylamino)pyridine (Flupirtine).

参考文献中间体

合成目标

【1】 Thiele, K.; Steinmetz, G.; Bebenburg, W.v.; Chem Ztg 1979, 103, 10, 387.
【2】 Bebenburg, W.v.; Engel, J.; Sheldrick, W.S.; Thiele, K.; Chem Ztg 1981, 105, 10, 217.
【3】 Castaner, J.; Serradell, M.N.; Blancafort, P.; Flupirtine. Drugs Fut 1983, 8, 9, 773.

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)	13574	2,6-Dichloro-3-nitropyridine	16013-85-7	C₅H₂Cl₂N₂O₂	详情	详情
(II)	13575	6-Chloro-3-nitro-2-pyridinamine; 2-Amino-6-chloro-3-nitropyridine; 6-Chloro-3-nitro-2-pyridinylamine	27048-04-0	C₅H₄ClN₃O₂	详情	详情
(III)	31095	4-fluorobenzylamine; (4-fluorophenyl)methanamine	140-75-0	C₇H₈FN	详情	详情
(IV)	13576	N(6)-(4-Fluorobenzyl)-3-nitro-2,6-pyridinediamine; N-(6-Amino-5-nitro-2-pyridinyl)-N-(4-fluorobenzyl)amine		C₁₂H₁₁FN₄O₂	详情	详情
(V)	13577	N(6)-(4-Fluorobenzyl)-2,3,6-pyridinetriamine; 2-Amino-6-[(4-fluorobenzyl)amino]-3-pyridinylamine		C₁₂H₁₃FN₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

D-19050 can be obtained in a 5-step synthesis starting from 2,6-dichloropyridine (I): Compound (I) is nitrated with HNO3/H2SO4 yielding 2,6-dichloro-3-nitropyridine (II). Subsequent reaction with ammonia and 4-fluorobenzylamine leads to 2-amino-3-nitro-6-(4-fluorobenzylamino)pyridine (IV), which is hydrogenated using Raney Nickel as catalyst to the corresponding 3-amino derivative (V). This is not isolated, but reacted with (prop-1-en-3-yl)chloroformate to give D-19050.

参考文献中间体

合成目标

【1】 Engel, J.; Emig, P.; Szelenyi, I.; Nickel, B.; Weischer, K.H.; D-19050. Drugs Fut 1989, 14, 6, 511.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	31095	4-fluorobenzylamine; (4-fluorophenyl)methanamine	140-75-0	C₇H₈FN	详情	详情
(I)	13573	2,6-Dichloropyridine	2402-78-0	C₅H₃Cl₂N	详情	详情
(II)	13574	2,6-Dichloro-3-nitropyridine	16013-85-7	C₅H₂Cl₂N₂O₂	详情	详情
(III)	13575	6-Chloro-3-nitro-2-pyridinamine; 2-Amino-6-chloro-3-nitropyridine; 6-Chloro-3-nitro-2-pyridinylamine	27048-04-0	C₅H₄ClN₃O₂	详情	详情
(IV)	13576	N(6)-(4-Fluorobenzyl)-3-nitro-2,6-pyridinediamine; N-(6-Amino-5-nitro-2-pyridinyl)-N-(4-fluorobenzyl)amine		C₁₂H₁₁FN₄O₂	详情	详情
(V)	13577	N(6)-(4-Fluorobenzyl)-2,3,6-pyridinetriamine; 2-Amino-6-[(4-fluorobenzyl)amino]-3-pyridinylamine		C₁₂H₁₃FN₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

D-19274 can be obtained in a 6-step synthesis starting from 2,6-dichloropyridine (I). Compound (I) is nitrated with HNO3/H2SO4 yielding 2,6-dichloro-3-nitropyridine (II). Subsequent reaction with ammonia and 4-fluorobenzylamine leads to 2-amino-3-nitro-6-(4-fluorobenzylamino)pyridine (IV), which is hydrogenated using Raney Nickel as catalyst to the corresponding 3-amino derivative (V), which reacts with 2-bromoethyl chloroformate to 2-bromoethyl [N-(2-amino-6-(4-fluorobenzylamino)pyridin-3-yl)]carbamate hydrochloride (VI). (VI) is then treated with excess NaOH at 35 C, followed by treatment with isopropanol HCl to give the desired D-19274.

参考文献中间体

合成目标

【1】 Engel, J.; Emig, P.; Nickel, B.; Szelenyi, I. (Asta Medica AG); 3-(N-heterocyclyl)-2,6-diaminopyridines and N-oxides, their preparation and their use as medicines. DE 3915184; EP 0343429; JP 1990017186; US 4923858 .
【2】 Emig, P.; Engel, J.; Nickel, B.; Szelenyi, I.; Werner, U.; D-19274. Drugs Fut 1990, 15, 3, 223.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	31095	4-fluorobenzylamine; (4-fluorophenyl)methanamine	140-75-0	C₇H₈FN	详情	详情
	63775	1-bromo-2-[(chlorocarbonyl)oxy]ethane		C₃H₄BrClO₂	详情	详情
(I)	13573	2,6-Dichloropyridine	2402-78-0	C₅H₃Cl₂N	详情	详情
(II)	13574	2,6-Dichloro-3-nitropyridine	16013-85-7	C₅H₂Cl₂N₂O₂	详情	详情
(III)	13575	6-Chloro-3-nitro-2-pyridinamine; 2-Amino-6-chloro-3-nitropyridine; 6-Chloro-3-nitro-2-pyridinylamine	27048-04-0	C₅H₄ClN₃O₂	详情	详情
(IV)	13576	N(6)-(4-Fluorobenzyl)-3-nitro-2,6-pyridinediamine; N-(6-Amino-5-nitro-2-pyridinyl)-N-(4-fluorobenzyl)amine		C₁₂H₁₁FN₄O₂	详情	详情
(V)	13577	N(6)-(4-Fluorobenzyl)-2,3,6-pyridinetriamine; 2-Amino-6-[(4-fluorobenzyl)amino]-3-pyridinylamine		C₁₂H₁₃FN₄	详情	详情
(VI)	13578	2-bromoethyl 2-amino-6-[(4-fluorobenzyl)amino]-3-pyridinylcarbamate		C₁₅H₁₆BrFN₄O₂	详情	详情

Extended Information