Dimethylformamide → HCID 178473714, compound

HRID 2366929Notes

Reaction equation

HRID 2366929 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].CN(C)C=O.C[Si]([N:33]=[N+:34]=[N-:35])(C)C>[Cu]I.CO>[CH3:3][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]3[N:33]=[N:34][NH:35][CH:18]=3)[CH:15]=2)[N:10]([C:19](=[O:21])[CH3:20])[C@@H:9]([CH3:22])[CH2:8]1)[CH3:1]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 78378AzidotrimethylsilaneHCID 86669236HCID 86669236, compound

Product 1

HCID 178473714HCID 178473714, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

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). Trimethylsilyl azide (0.059 mL, 0.509 mmol) was added and the resulting mixture was stirred under microwave irradiation at 100° C. for 5 h then cooled to room temperature. The solution was partitioned between AcOEt and water/brine (1/1) and the layers were separated. The aqueous phase was extracted three times with AcOEt and the combined organic phases were washed with water then brine, dried over MgSO4 and concentrated in vacuo. The residue was purified using MDAP (modifier: ammonium bicarbonate). The appropriate fractions were concentrated in vacuo and the residue dissolved in DCM. The organic phase was dried using a phase separator then concentrated in vacuo to give 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (30 mg, 0.084 mmol, 33.0% yield) as a white foam.

Workup

  1. customfor a preparation
  2. temperaturethen cooled to room temperature
  3. customThe solution was partitioned between AcOEt and water/brine (1/1)
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted three times with AcOEt
  6. washthe combined organic phases were washed with water
  7. dry with materialbrine, dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified
  10. concentrationThe appropriate fractions were concentrated in vacuo
  11. dissolutionthe residue dissolved in DCM
  12. customThe organic phase was dried
  13. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-a464790e83cf42c9b6aa2b38a8b86ea4
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…