三乙胺 → 10-Chloro-2-(3-furylmethyl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one

HRID 2234411

反应方程式

HRID 2234411 反应方程式
[O:1]1[CH:5]=[CH:4][C:3]([CH2:6][NH2:7])=[CH:2]1.[Cl:8][C:9]1[N:14]=[C:13](Cl)[C:12]([N:16]([CH3:21])[C:17](=[O:20])[CH:18]=[CH2:19])=[CH:11][N:10]=1.C(N(CC)CC)C>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4].C(Cl)Cl>[Cl:8][C:9]1[N:10]=[C:11]2[C:12]([N:16]([CH3:21])[C:17](=[O:20])[CH2:18][CH2:19][N:7]2[CH2:6][C:3]2[CH:4]=[CH:5][O:1][CH:2]=2)=[CH:13][N:14]=1

参与物

6

反应物 3

HCID 8471三乙胺HCID 27761973-呋喃基甲胺HCID 86617580N-(2,4-dichloropyrimidin-5-yl)-N-methyl-prop-2-enamide2 次

产物 1

HCID 8661758110-Chloro-2-(3-furylmethyl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one收率 15.3%

试剂、催化剂与溶剂 2

HCID 76524Titanium tetraethoxide催化剂HCID 6344二氯甲烷溶剂

实验过程

3-Furylmethylamine (Maybridge; 175 mg, 1.8 mmol), N-(2,4-dichloropyrimidin-5-yl)-N-methyl-prop-2-enamide (Intermediate 113; 347 mg, 1.5 mmol), Triethylamine (420 μL, 3 mmol), Titanium Tetra-ethoxide (157 μL, 0.75 mmol) and DCM (5 mL) were combined and stirred at room temp for 1 hr, heated at 40° C. overnight then cooled to room temperature. The reaction mixture was washed with water then gravity filtered through a PTFE cup, the aqueous layer containing the titanium emulsion was washed with further DCM (3×10 mL) and the combined organic solutions gravity filtered through a PTFE cup and solvents evaporated. The residue was dissolved in DCM and purified by chromatographic separation on silica eluting with a shallow gradient (25 column volumes) of 10-50% Ethyl Acetate/iso-hexane. Product containing fractions were combined and evaporated to give the title compound as a yellow gum (67 mg, 15%)

后处理

  1. temperatureheated at 40° C. overnight
  2. temperaturethen cooled to room temperature
  3. washThe reaction mixture was washed with water
  4. filtrationgravity filtered through a PTFE cup
  5. additionthe aqueous layer containing the titanium emulsion
  6. washwas washed with further DCM (3×10 mL)
  7. filtrationthe combined organic solutions gravity filtered through a PTFE cup and solvents
  8. customevaporated
  9. dissolutionThe residue was dissolved in DCM
  10. custompurified by chromatographic separation on silica eluting with a shallow gradient (25 column volumes) of 10-50% Ethyl Acetate/iso-hexane
  11. additionProduct containing fractions
  12. customevaporated

来源与证据

ORD记录
ord-b1e0e6425e64402598d0e032e30bea48
来源数据集
uspto-grants-2010_05
专利号
US07709471B2

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