Dimethylformamide → HCID 178473711, compound

HRID 2041785Notes

Reaction equation

HRID 2041785 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]#[CH:15])=[CH:11][CH:12]=2)[C@H:7]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][N:18]=2)[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2].CN(C)C=O.C[Si]([N:34]=[N+:35]=[N-:36])(C)C>[Cu]I.CO>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:34]=[N:35][NH:36][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][N:18]=2)[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 78378AzidotrimethylsilaneHCID 86669452HCID 86669452, compound

Product 1

HCID 178473711HCID 178473711, compoundYield 0.928%

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 (2S,4R)-1-acetyl-6-ethynyl-2-methyl-N-(5-methyl-2-pyridinyl)-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see Intermediate 110) (57 mg, 0.178 mmol) and copper(I) iodide (3.40 mg, 0.018 mmol) then filled with N,N-dimethylformamide (DMF) (1.8 mL) and methanol (0.2 mL) and the resulting mixture was treated with trimethylsilyl azide (0.095 mL, 0.714 mmol). The flask was flushed with nitrogen then the mixture was stirred at 100° C. for 2 h under microwave irradiation then cooled to room temperature. Most of the methanol was removed in vacuo and the residue partitioned between AcOEt and water. The layers were separated and the aqueous layer was extracted with AcOEt. The combined organic phases were washed with water, dried over MgSO4 and concentrated in vacuo. Purification of the residue by MDAP (modifier: ammonium bicarbonate) gave (2S,4R)-1-acetyl-2-methyl-N-(5-methyl-2-pyridinyl)-6-(1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydro-4-quinolinamine (0.6 mg, 1.655 μmol, 0.928% yield) as a colourless solid.

Workup

  1. customThe flask was flushed with nitrogen
  2. temperaturethen cooled to room temperature
  3. customMost of the methanol was removed in vacuo
  4. customthe residue partitioned between AcOEt and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with AcOEt
  7. washThe combined organic phases were washed with water
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue by MDAP (modifier: ammonium bicarbonate)

Sources & evidence

ORD record
ord-1c9dde24b60f46b498732e2916b74626
Source dataset
uspto-grants-2013_11
Patent number
US08580957B2

Reaction notes

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