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【结 构 式】 
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【分子编号】14614 【品名】2-Amino-4-picoline; 4-Methyl-2-pyridinamine; 4-Methyl-2-pyridinylamine; 2-Amino-4-methylpyridine 【CA登记号】695-34-1 |
【 分 子 式 】C6H8N2 【 分 子 量 】108.143 【元素组成】C 66.64% H 7.46% N 25.9% |
合成路线1
该中间体在本合成路线中的序号：(IV)The reaction of rifamycin S (I) with pyridine perbromide (II) in 2-propanol/chloroform (70/30) mixture at 0 C gives 3-bromorifamicin S (III), which is then condensed with 2-amino-4-methyl-pyridine (IV) at 10 C. The o-quinoniminic compound (V) is then obtained. This compound is finally reduced with ascorbic acid.
| 【1】 US 262123 . |
| 【2】 de Angelis, L.; L-105. Drugs Fut 1982, 7, 4, 260. |
| 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) | 31943 | Rifamycin S; (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate | C37H45NO12 | 详情 | 详情 | |
| (III) | 31944 | (7S,11S,12R,13S,14R,15R,16R,17S,18S)-26-bromo-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.1(4,7).0(5,28)]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl acetate; 3-bromorifamicin S | C37H44BrNO12 | 详情 | 详情 | |
| (IV) | 14614 | 2-Amino-4-picoline; 4-Methyl-2-pyridinamine; 4-Methyl-2-pyridinylamine; 2-Amino-4-methylpyridine | 695-34-1 | C6H8N2 | 详情 | 详情 |
| (V) | 31945 | (7S,11S,12R,13S,14R,15R,16R,17S,18S)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22,30-octamethyl-6,23,36-trioxo-8,37-dioxa-24,27,33-triazahexacyclo[23.10.1.1(4,7).0(5,35).0(26,34).0(27,32)]heptatriaconta-1(35),2,4,9,19,21,24,26(34),28,30,32-undec | C43H49N3O11 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The reaction of 2-(3-benzoylphenyl)propionic acid (I) with SOCl2 or PCl3 gives the corresponding acyl chloride (II), which is then condensed with 4-methylpyridine-2-amine (III) by means of 4-methylpyridine in pyridine.
| 【1】 Vega, A.; Prieto, J.; Moragues, J. (Fordonal SL); Procedimiento para la preparacion de una amida de la 2-amino-4-metylpiridina. BE 0882711; ES 8102556; IT 1130573 . |
| 【2】 Vega Noverola, A.; Prieto Soto, J.; Spickett, R.G.W.; Amide derivs. of 3-benzoyl-phenylalkanoic acids. GB 1436502 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 31150 | 4-methylpyridine | 108-89-4 | C6H7N | 详情 | 详情 |
| (I) | 24290 | 2-(3-benzoylphenyl)propionic acid | 22071-15-4 | C16H14O3 | 详情 | 详情 |
| (II) | 24291 | 2-(3-benzoylphenyl)propanoyl chloride | C16H13ClO2 | 详情 | 详情 | |
| (III) | 14614 | 2-Amino-4-picoline; 4-Methyl-2-pyridinamine; 4-Methyl-2-pyridinylamine; 2-Amino-4-methylpyridine | 695-34-1 | C6H8N2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)The diazonium salt from 2-amino-4-methylpyridine (I) is converted to 2-hydroxy-4-methylpyridine (II), which is nitrated to give 2-hydroxy-4-methyl-3-nitropyridine (III). Conversion to 2-chloro-4-methyl-3-nitropyridine (IV) is effected with phosphorous oxychloride and phosphorous pentachloride. Reduction of (IV) with hydrogen/Raney Nickel provides 3-amino-2-chloro-4-methylpyridine (V), which is condensed with 2-chloronicotinoyl chloride to give 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide (VI). Treatment with cyclopropylamine affords N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide (VII), which is cyclized in the presence of sodium hydride to yield nevirapine.
| 【1】 Hargrave, K.D.; Grozinger, K.G.; Proudfoot, J.R.; et al.; Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones. J Med Chem 1991, 34, 7, 2231-41. |
| 【2】 Riska, P.S.; Johnstone, J.N.; Silverstein, H.H.; Hattox, S.E.; Norris, S.H.; St. George, R.; Grob, P.M.; Hargrave, K.D.; Nevirapine. Drugs Fut 1992, 17, 10, 887. |
| 【3】 Hargrave, K.D.; Merluzzi, V.J.; Labadia, M.; et al.; Inhibition of HIV-1 replication by a non-nucleoside reverse transcriptase inhibitor. Science 1990, 250, 4986, 1411-3. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15224 | 2-chloronicotinoyl chloride | 49609-84-9 | C6H3Cl2NO | 详情 | 详情 | |
| (I) | 14614 | 2-Amino-4-picoline; 4-Methyl-2-pyridinamine; 4-Methyl-2-pyridinylamine; 2-Amino-4-methylpyridine | 695-34-1 | C6H8N2 | 详情 | 详情 |
| (II) | 14615 | 4-methyl-2-pyridinol | C6H7NO | 详情 | 详情 | |
| (III) | 14616 | 4-Methyl-3-nitro-pyridin-2-ol; 4-Methyl-3-nitro-2-pyridinol | 21901-18-8 | C6H6N2O3 | 详情 | 详情 |
| (IV) | 14617 | 2-chloro-4-methyl-3-nitropyridine | 23056-39-5 | C6H5ClN2O2 | 详情 | 详情 |
| (V) | 14618 | 2-chloro-4-methyl-3-pyridinamine; 2-chloro-4-methyl-3-pyridinylamine | 133627-45-9 | C6H7ClN2 | 详情 | 详情 |
| (VI) | 14619 | 2-chloro-N-(2-chloro-4-methyl-3-pyridinyl)nicotinamide | C12H9Cl2N3O | 详情 | 详情 | |
| (VII) | 14620 | N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)nicotinamide; N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide | 133627-47-1 | C15H15ClN4O | 详情 | 详情 |