反应详情

To a suspension of 5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (for example available from UkrOrgSynthesis Building Blocks; 264 mg, 1.22 mmol) in dichloromethane (5.00 ml) at room temperature was added oxalyl chloride (0.292 ml, 3.33 mmol) followed by one drop of N,N-dimethylformamide (DMF) and the resulting mixture was stirred for 1 h at room temperature. The solvent was removed in vacuo and the residue co-evaporated with toluene then left for 5 min under vacuum. To a solution of 1,1-dimethylethyl 6-[(hydroxyamino)(imino)methyl]-5-methyl-1-(4-oxoheptyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 27; 232 mg, 0.556 mmol) in DMF (5 ml) was added triethylamine (0.116 ml, 0.833 mmol) then half of the acid chloride (i.e. 2 ml out of the 4 ml of DMF used to dissolve it). The mixture was stirred for 1 h at room temperature and heated at 120° C. for 100 min. The mixture was cooled to room temperature and most of the solvent concentrated in vacuo. The residue was dissolved in ethyl acetate and the solution washed with saturated sodium bicarbonate, dried over MgSO4 and concentrated in vacuo to give a residue (ca. 310 mg) which was purified by flash chromatography, eluting with 5-25% ethyl acetate in cyclohexane to give the title compound (102 mg) as a white foam

1. customat room temperature
2. customThe solvent was removed in vacuo
3. waitthe residue co-evaporated with toluene then left for 5 min under vacuum
4. dissolutionto dissolve it)
5. stirringThe mixture was stirred for 1 h at room temperature
6. temperatureheated at 120° C. for 100 min
7. temperatureThe mixture was cooled to room temperature and most of the solvent
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in ethyl acetate
10. washthe solution washed with saturated sodium bicarbonate
11. dry with materialdried over MgSO4
12. concentrationconcentrated in vacuo