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以D-脯氨酸、2-甲基丙烯酰氯为原料,通过酰化得到(2R)-1-(2-甲基丙烯酰氯)四氢吡咯-2-羧酸(2),2与NBS环合得到(3R)-溴甲基-3-甲基四氢吡咯并[2,1-C][1,4]-噁嗪-1,4-二酮(3),3经盐酸水解得(R)-3-溴-2-羟基-2-甲基丙酸(4),4与氯化亚砜、3-三氟甲基-4-硝基苯胺酰化得到(S)-3-溴-2-羟基-2-甲基-N[-4-硝基(-三氟甲基苯基)]丙酰胺(5),5再与对乙酰氨基酚缩合得到Ostarine(1)。合成选择性雄性受体调剂Ostarine,反应总收率为28.4%。中间体和目标化合物的结构经1H-NMR确证。该工艺路线简单,反应试剂和原料价廉易得,操作方便,适合于工业化生产。
(2R) -1- (2-methacryloyl chloride) tetrahydropyrrole-2-carboxylic acid (2), 2 and NBS ring were obtained from D-proline and 2-methacryloyl chloride by acylation (3R) -bromomethyl-3-methyltetrahydropyrrolo [2,1-c] [1,4] -oxazine-1,4-dione (3) (4), 4 with thionyl chloride, 3-trifluoromethyl-4-nitroanilide to give (S) -3-bromo -2-hydroxy-2-methyl-N [-4-nitro (-trifluoromethylphenyl)] propanamide (5), which is condensed with acetaminophen to give Ostarine (1). Ostarine was synthesized by selective synthesis of male acceptor and the total reaction yield was 28.4%. The structures of intermediates and target compounds were confirmed by1H-NMR. The process route is simple, reagents and raw materials cheap, easy to operate, suitable for industrial production.