A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate
A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate
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DOI：
10.1021/op7001326
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发表时间：
2007-09-01
影响因子：
3.4
通讯作者：
Toczko, Matthew A.
中科院分区：
文献类型：
--
作者：
Boros, Eric E.;Burova, Svetlana A.;Toczko, Matthew A.
以5-溴-2-甲氧基吡啶（8）和4-氟苯甲醛（9）为原料，合成了3-氨基-5-（4-氟苄基）-2-吡啶甲酸甲酯（1b）。该方法的关键步骤包括8的锂-溴交换，将所得锂盐添加到醛9中，吡啶酮12的区域选择性硝化，以及溴吡啶15 b的Pd催化的烷氧基羰基化。五步合成的总产率为23%;分离中间体10、12、13、15 b和最终产物Ib中心点HCl，为可过滤固体。化合物1a、B是合成7-苄基萘啶酮（例如，2)和相关的HIV-1整合酶抑制剂。
A scaleable synthesis of methyl 3-amino-5-(4-fiuorobenzy1)-2-pyridinecarboxylate (1b), starting from 5-bromo-2-methoxypyridine (8) and 4-fluorobenzaidehyde (9), is described. Key steps in the process include lithium-bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselective nitration of pyridone 12, and Pd-catalyzed alkoxycarbonylation of bromopyridine 15b. Overall yield of the five-stage synthesis was 23%; intermediates 10, 12, 13, 15b, and final product 1b center dot HCl were isolated as filterable solids. Compounds 1a,b are important intermediates in the synthesis of 7-benzylnaphthyridinones (e.g., 2) and related HIV-1 integrase inhibitors.