Methanol → methyl {4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-1,2,3-triazol-1-yl}acetate

HRID 2366871Notes

Reaction equation

HRID 2366871 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:23])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[CH:18])[CH:15]=2)[N:10]([C:19](=[O:21])[CH3:20])[C@@H:9]([CH3:22])[CH2:8]1)[CH3:3].CO.[N:26]([CH2:29][C:30]([O:32][CH3:33])=[O:31])=[N+:27]=[N-:28]>CN(C)C=O.[Cu]I>[C:19]([N:10]1[C:11]2[C:16](=[CH:15][C:14]([C:17]3[N:28]=[N:27][N:26]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH:18]=3)=[CH:13][CH:12]=2)[C@H:7]([NH:6][C:5]([O:4][CH:2]([CH3:1])[CH3:3])=[O:23])[CH2:8][C@@H:9]1[CH3:22])(=[O:21])[CH3:20]

Participants

6

Reactant 3

HCID 887MethanolHCID 4020482Methyl 2-azidoacetateHCID 86669236HCID 86669236, compound

Product 1

HCID 68185402methyl {4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-1,2,3-triazol-1-yl}acetateYield 96%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (408 mg, 1.298 mmol) in N,N-dimethylformamide (DMF) (8 mL) and methanol (0.9 mL) were successively added methyl azidoacetate (299 mg, 2.60 mmol) and copper(I) iodide (12.36 mg, 0.065 mmol). The resulting mixture was stirred at 100° C. under microwave irradiation for 2 h then cooled to room temperature and partitioned between brine and AcOEt. The layers were separated. The aqueous phase was extracted with EtOAc (3×) and the combined organic layers were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue on SP4 using a 25 G silica cartridge (gradient: 2 to 10% MeOH in DCM) gave methyl {4-[(2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinyl]-1H-1,2,3-triazol-1-yl}acetate (468 mg, 1.046 mmol, 96%) as a viscous yellow oil.

Workup

  1. temperaturethen cooled to room temperature
  2. custompartitioned between brine and AcOEt
  3. customThe layers were separated
  4. extractionThe aqueous phase was extracted with EtOAc (3×)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over a Na2SO4 cartridge
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue on SP4

Sources & evidence

ORD record
ord-5e58df43176d492e86c69de13b60ef31
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…