反应详情

温度

100 °C

A flask was charged with 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (80 mg, 0.254 mmol) and copper(I) iodide (2.423 mg, 0.013 mmol) then filled with N,N-dimethylformamide (DMF) (1.8 mL) and methanol (0.200 mL). 1,1-Dimethylethyl (2-azidoethyl)carbamate (for a preparation, see Intermediate 78) (95 mg, 0.509 mmol) was added and the resulting mixture was stirred under microwave irradiation at 100° C. for 2 h then cooled to room temperature. The reaction mixture was partitioned between EtOAc and brine and the layers were separated. The aqueous phase was extracted with EtOAc (3×) and the combined organic phases were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient: 5 to 25% (10% MeOH in DCM) in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-1,2,3-triazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (108 mg, 0.216 mmol, 85% yield) as a pale yellow foam. LCMS (method A): Retention time 0.95 min, [M+H]+=501.26

1. customfor a preparation
2. additionwas added
3. temperaturethen cooled to room temperature
4. customThe reaction mixture was partitioned between EtOAc and brine
5. customthe layers were separated
6. extractionThe aqueous phase was extracted with EtOAc (3×)
7. washthe combined organic phases were washed with brine
8. dry with materialdried over a Na2SO4 cartridge
9. concentrationconcentrated in vacuo
10. customPurification of the residue on SP4