|
【结 构 式】 
|
【分子编号】13575 【品名】6-Chloro-3-nitro-2-pyridinamine; 2-Amino-6-chloro-3-nitropyridine; 6-Chloro-3-nitro-2-pyridinylamine 【CA登记号】27048-04-0 |
【 分 子 式 】C5H4ClN3O2 【 分 子 量 】173.55848 【元素组成】C 34.6% H 2.32% Cl 20.43% N 24.21% O 18.44% |
合成路线1
该中间体在本合成路线中的序号：(II)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).
| 【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：(III)D 7175 can be obtained in a 5-step synthesis starting from 2,e-dichloropyridine (I). Compound (I) is nitrated with HNO3/H2SO4 yielding 2,6-dichloro-3-nitropyridine (II). Subsequent reaction with ammonia and benzylamine leads to 2-amino-3-nitro-6-benzylaminopyridine (IV), which is hydrogenated using Raney Nickel as catalyst te the corresponding 3-amino derivative (V), which reacts without isolation with ethyl chloroformiate to D-7175.
| 【1】 Bebengurg, W.; Engek, J.; Heese, J.; Thiele, K. (Degussa AG); 2-Amino-3-acylamino-6-benzylaminopyridine derivatives having antiepileptic action. DE 3337593 . |
| 【2】 Molliere, M.; Engel, J.; Emig, P.; D-7175. Drugs Fut 1988, 13, 1, 22. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15147 | Benzylamine; Phenylmethanamine | 100-46-9 | C7H9N | 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) | 21572 | N(6)-benzyl-3-nitro-2,6-pyridinediamine | C12H12N4O2 | 详情 | 详情 | |
| (V) | 21573 | 2-amino-6-(benzylamino)-3-pyridinylamine | C12H14N4 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)2,6-Dichloro-3-nitropyridine (I) reacts with ammonia and p-chlorobenzylamine (III) yielding 2-amino-3-nitro-6-(4-chlorobenzyl)aminopyridine (IV). D-9389 is obtained after hydrogenation and reaction with ethylchloroformate.
| 【1】 Bebengurg, W.; Engek, J.; Heese, J.; Thiele, K. (Degussa AG); 2-Amino-3-acylamino-6-benzylaminopyridine derivatives having antiepileptic action. DE 3337593 . |
| 【2】 Molliere, M.; Emig, P.; Szelenyi, I.; Engel, J.; D-9389. Drugs Fut 1988, 13, 8, 717. |
| 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) | 23378 | (4-chlorophenyl)methanamine; 4-chlorobenzylamine | 104-86-9 | C7H8ClN | 详情 | 详情 |
| (IV) | 23379 | N-(6-amino-5-nitro-2-pyridinyl)-N-(4-chlorobenzyl)amine; N(6)-(4-chlorobenzyl)-3-nitro-2,6-pyridinediamine | C12H11ClN4O2 | 详情 | 详情 | |
| (V) | 23380 | 2-amino-6-[(4-chlorobenzyl)amino]-3-pyridinylamine; N(6)-(4-chlorobenzyl)-2,3,6-pyridinetriamine | C12H13ClN4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)D-11208 is obtained in a five step synthesis: 2,6-Dichloro-3-nitropyridine (I) reacts with ammonia to give 2-amino-3-nitro-6-chloropyridine (II). Subsequent condensation with 4-trifluoromethyl benzylamine (III) yields 2-amino-3-nitro-6-(4-trifluoromethyl)aminopyridine (IV). Hydrogenation with Raney Nickel as catalyst and reaction with ethyl chloroformiate yields D-11208.
| 【1】 Bebengurg, W.; Engek, J.; Heese, J.; Thiele, K. (Degussa AG); 2-Amino-3-acylamino-6-benzylaminopyridine derivatives having antiepileptic action. DE 3337593 . |
| 【2】 Engel, J.; Molliere, M.; Emig, P.; Szelenyi, I.; D-11208. Drugs Fut 1988, 13, 9, 817. |
| 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) | 21925 | [4-(trifluoromethyl)phenyl]methanamine; 4-(trifluoromethyl)benzylamine | 3300-51-4 | C8H8F3N | 详情 | 详情 |
| (IV) | 23270 | N-(6-amino-5-nitro-2-pyridinyl)-N-[4-(trifluoromethyl)benzyl]amine; 3-nitro-N(6)-[4-(trifluoromethyl)benzyl]-2,6-pyridinediamine | C13H11F3N4O2 | 详情 | 详情 | |
| (V) | 23271 | 2-amino-6-[[4-(trifluoromethyl)benzyl]amino]-3-pyridinylamine; N(6)-[4-(trifluoromethyl)benzyl]-2,3,6-pyridinetriamine | C13H13F3N4 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(III)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.
| 【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6
该中间体在本合成路线中的序号：(III)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.
| 【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 |