N-甲基吡咯烷酮 → (2S,4R)-1-(tert-butoxycarbonyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxylic acid

HRID 627770

反应方程式

HRID 627770 反应方程式
[C:1]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[C:18]1[C:27]([C:28]2[S:29][CH:30]=[CH:31][CH:32]=2)=[N:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[N:19]=1.CC(C)([O-])C.[Na+].C[N:40]1C(=O)[CH2:43][CH2:42][CH2:41]1>>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([O:16][C:18]2[C:27]([C:28]3[S:29][C:30]4[CH:31]=[CH:32][CH:43]=[CH:42][C:41]=4[N:40]=3)=[N:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:2])([CH3:7])([CH3:6])[CH3:5]

参与物

5

反应物 4

HCID 13387N-甲基吡咯烷酮HCID 88804Boc-L-羟脯氨酸HCID 28016552-Chloro-3-(2-thienyl)quinoxalineHCID 23676156叔丁醇钠

产物 1

HCID 67296859(2S,4R)-1-(tert-butoxycarbonyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxylic acid

实验过程

(2S,4R)—N-Boc-4-hydroxyproline can be reacted with 2-chloro-3-(thiophen-2-yl)quinoxaline in NMP, in the presence of sodium t-butoxide, to produce (2S,4R)-1-(tert-butoxycarbonyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-2-carboxylic acid. Methyl tertiary butyl ether (MTBE) and water can then be added. The aqueous layer is separated, washed, and then HCl is added, followed by extraction with MTBE. The extracted product can be mixed with diisopropylethylamine (DIPEA) and HATU (CAS #148893-10-1), and then reacted with (1R,2S)-ethyl-1-amino-2-vinylcyclopropanecarboxylate tosylate salt in dimethylformide (DMF) and toluene. The reaction produces (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(3-(benzo[d]thiazol-2-yl)quinoxalin-2-yloxy)pyrrolidine-1-carboxylate, which can be extracted with MTBE and washed with HCl, further extracted, washed, dried, and dissolved in 2-propanol.

来源与证据

ORD记录
ord-b21eb6ba16fd4d9198c8135e6ce64aeb
来源数据集
uspto-grants-2016_04
专利号
US09309279B2

关联笔记

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