N,N'-Dimethylethylenediamine → HCID 68504614, compound

HRID 876366Notes

Reaction equation

HRID 876366 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:11]([O:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH2:10][CH2:9][N:8]([CH3:20])[CH2:7][C:6]=2[CH:21]=1.CN[CH2:24][CH2:25][NH:26][CH3:27].P([O-])([O-])([O-])=[O:29].[K+].[K+].[K+].O1CCO[CH2:38][CH2:37]1>ClCCl.[Cu]I>[F:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][CH:11]2[CH2:10][CH2:9][N:8]([CH3:20])[CH2:7][C:6]3[CH:21]=[C:2]([N:26]4[CH:27]=[CH:38][CH:37]=[CH:24][C:25]4=[O:29])[CH:3]=[CH:4][C:5]2=3)=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 68500621HCID 68500621, compound2×

Product 1

HCID 68504614HCID 68504614, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of the bromide from Step E (0.4 g, 1.1 mmol, slightly impure) and 2-hydroxy-pyridine (0.13 g, 1.37 mmol) from Step E in 1,4-dioxane (1.4 mL) were added N,N′-dimethylethylenediamine (50 μL, 0.46 mmol) and potassium phosphate (0.48 g, 2.30 mmol). The mixture was purged with argon for ˜10 minutes, and copper (I) iodide (40 mg, 0.2 mmol) was added to it. The reaction was heated at 110° C. for 12 hours. After cooling to room temperature, the reaction mixture was diluted with dichloromethane, washed with water and brine, dried over sodium sulfate, filtered and concentrated to give the crude product. Purification by preparative thin layer chromatography (90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) twice gave the desired product (144 mg, 36%) as an off-white foam: 1H NMR (CDCl3, 300 MHz) δ 7.45-7.26 (m, 3H), 7.25-7.21 (m, 2H), 6.95 (t, J=8.6 Hz, 2H), 6.88-6.83 (m, 2H), 6.64 (d, J=9.2 Hz, 1H), 6.30-6.25 (m, 1H), 5.36-5.30 (m, 1H), 4.05-3.83 (m, 2H), 3.35-3.20 (m, 1H), 3.10-3.00 (m, 1H), 2.37 (s, 3H), 2.20-2.13 (m, 2H).

Workup

  1. customThe mixture was purged with argon for ˜10 minutes
  2. temperatureAfter cooling to room temperature
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product
  8. customPurification by preparative thin layer chromatography (90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide)

Sources & evidence

ORD record
ord-29279cb24c584efb830e444f250af343
Source dataset
uspto-grants-2015_03
Patent number
US08987252B2

Reaction notes

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