Propargyl bromide → 1-(4-Amino-quinazolin-7-ylmethyl)-4-prop-2-ynyl-piperazin-2-one

HRID 1432963Notes

Reaction equation

HRID 1432963 reaction equation
[CH2:1](Br)[C:2]#[CH:3].[NH2:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([CH2:16][N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C:18]3=[O:23])=[CH:13][CH:14]=2)[N:9]=[CH:8][N:7]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[NH2:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([CH2:16][N:17]3[CH2:22][CH2:21][N:20]([CH2:3][C:2]#[CH:1])[CH2:19][C:18]3=[O:23])=[CH:13][CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 11430Potassium CarbonateHCID 179851741-(4-Aminoquinazoline-7-ylmethyl)piperazine-2-one

Product 1

HCID 538421351-(4-Amino-quinazolin-7-ylmethyl)-4-prop-2-ynyl-piperazin-2-oneYield 68%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Propargyl bromide (0.29 g, 1.95 mmol) is added to a solution containing 1-(4-amino-quinazolin-7-ylmethyl)-piperazin-2-one (0.5 g, 1.95 mmol), EXAMPLE 72, and K2CO3 (0.40 g, 2.93 mmol) in DMSO (10 mL) at ambient temperature. After 15 min, the reaction mixture is partitioned between aqueous NaHCO3 (100 mL) and CH2Cl2 (100 mL) and the layers are separated. The aqueous phase is subsequently saturated with NaCl and extracted three times with CHCl3 (50 mL). The combined organic phase is washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue is purified by flash silica gel chromatography (CH2Cl2 to 10% MeOH/CH2Cl2) to provide 390 mg (68%) of the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ2.68 (m, 1H), 3.13-3.37 (m, 6H), 4.07 (app q, J=5.2 Hz, 1H), 4.63 (s, 2H), 7.28 (dd, J=8.4, 1.4 Hz, 1H), 7.42 (s, 1H), 7.72 (br s, 2H), 8.14 (d, J=8.4 Hz, 1H), 8.34 (s, 1H) ppm; MS (ISP loop): m/z 296 (M+H).

Workup

  1. customthe reaction mixture is partitioned between aqueous NaHCO3 (100 mL) and CH2Cl2 (100 mL)
  2. customthe layers are separated
  3. extractionextracted three times with CHCl3 (50 mL)
  4. washThe combined organic phase is washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by flash silica gel chromatography (CH2Cl2 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-0c45557d4f164c3ebe9fef975703d789
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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