Propargyl bromide → HCID 53990821, compound

HRID 1433002Notes

Reaction equation

HRID 1433002 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[CH2:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][C:19]1=[O:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:31](Br)[C:32]#[CH:33]>CC#N>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:10]=[C:9]1[CH2:17][N:18]1[CH2:23][CH2:22][N:21]([CH2:33][C:32]#[CH:31])[CH2:20][C:19]1=[O:24])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 544278362-(2-Oxo-piperazin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

Product 1

HCID 53990821HCID 53990821, compoundYield 70.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution containing 2-(2-oxo-piperazin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (4.3 g, 13.0 mmol), EXAMPLE 69, in CH3CN (250 mL) is cooled to 0° C. Potassium carbonate (1.98 g, 14.3 mmol) is added to the reaction mixture followed by propargyl bromide (1.55 g, 13.0 mmol). The mixture is slowly warmed to ambient temperature and maintained until complete consumption of starting material is observed by TLC (approx. 8 h). The mixture is concentrated to dryness and then partitioned between aqueous NaHCO3 (200 mL) and CH2Cl2 (200 mL) and the layers are separated. The aqueous phase is extracted twice with CH2Cl2 (100 mL) and the combined organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude residue is purified by flash silica gel chromatography (CH2Cl2 to 5% MeOH/CH2Cl2) to provide 3.38 g (70%) of the title compound as a pale yellow solid. 1H NMR (300 MHz, CDCl3) δ1.69 (s, 9H), 2.34 (t, J=2.4 Hz, 1H), 2.89 (m, 2H), 3.42 (s, 2H), 3.45 (d, J=2.4 Hz, 2H), 3.52 (m, 2H), 4.95 (d, J=1.4 Hz, 2H), 6.42 (br s, 1H), 7.88 (dd, J=5.8, 0.8 Hz, 1H), 8.41 (d, J=5.8 Hz, 1H), 8.78 (d, J=0.8 Hz, 1H) ppm; MS (EI): m/z 368 (M+).

Workup

  1. temperaturemaintained until complete consumption of starting material
  2. customis observed by TLC (approx. 8 h)
  3. concentrationThe mixture is concentrated to dryness
  4. custompartitioned between aqueous NaHCO3 (200 mL) and CH2Cl2 (200 mL)
  5. customthe layers are separated
  6. extractionThe aqueous phase is extracted twice with CH2Cl2 (100 mL)
  7. washthe combined organic phase is washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude residue is purified by flash silica gel chromatography (CH2Cl2 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-23a6a8bb5e6f484baf5714c6655cd598
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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