氰乙酸乙酯 → HCID 178470785，化合物

HRID 1056830笔记

反应方程式

HRID 1056830 反应方程式
[NH2:1][C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][CH2:10][C:4]=2[C:3]=1[C:11]([O:13]CC)=O.[CH2:16]([O:18][C:19](=[O:23])[CH2:20][C:21]#[N:22])[CH3:17].C([O-])(O)=O.[Na+]>O1CCOCC1>[OH:13][C:11]1[C:3]2[C:4]3[CH2:10][CH2:9][CH2:8][CH2:7][C:5]=3[S:6][C:2]=2[N:1]=[C:21]([CH2:20][C:19]([O:18][CH2:16][CH3:17])=[O:23])[N:22]=1

参与物

5

反应物 3

HCID 7764氰乙酸乙酯HCID 782622-氨基-4,5,6,7-四氢苯并噻酚-3-羧酸乙酯HCID 516892碳酸氢钠

产物 1

HCID 178470785HCID 178470785，化合物

试剂、催化剂与溶剂 1

HCID 312751,4-二氧六环溶剂

反应条件

温度
0 °C

实验过程

The ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (8.0 g, 0.0355 mol) and ethyl-2-cyanoacetate (8.03 g, 0.0710 mol) was dissolved in dioxane (250 ml). It was cooled to 0° C. To this reaction mixture, HCl gas was purged up to saturation (for 20 min, initially reaction mass becomes turbid and then becomes clears). Then reaction mass was stirred for 18 h at room temperature. After completion of the reaction it was cooled to 0° C. and basified with saturated NaHCO3 (pH=8). Further it was extracted with ethyl acetate (250 ml×3). Combined organic extracts were washed with water followed with brine. Separated organic layer was dried over anhy. Na2SO4, filtered and concentrated to get 9 g crude product. It was purified by column chromatography by using 100-200 mesh silica gel and 1-2% MeOH: DCM solvent system to give ethyl 2-(4-hydroxy-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-yl)acetate as yellow solid. Yield—(9.0 g, 86.71%); 1H-NMR: (400 MHz, CDCl3); δ=4.25-4.20 (q, 2H), 3.77 (s, 2H), 3.00-2.97 (m, 2H), 2.76-2.74 (m, 2H), 1.88-1.81 (m, 4H), 1.29-1.25 (t, 3H); LC-MS [M+H]=292.9.

后处理

  1. customTo this reaction mixture, HCl gas was purged up to saturation (for 20 min
  2. custominitially reaction mass
  3. customThen reaction mass
  4. customAfter completion of the reaction it
  5. extractionFurther it was extracted with ethyl acetate (250 ml×3)
  6. washCombined organic extracts were washed with water
  7. customSeparated organic layer was dried over anhy
  8. filtrationNa2SO4, filtered
  9. concentrationconcentrated
  10. customto get 9 g crude product
  11. customIt was purified by column chromatography

来源与证据

ORD记录
ord-95f42eb2a87c4c588605a0de1ba352a4
来源数据集
uspto-grants-2016_07
专利号
US09399647B2

反应笔记

加载中…