Triethylamine → N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]-2-methylacrylamide

HRID 507465Notes

Reaction equation

HRID 507465 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=1.CCN(CC)CC.[C:27](Cl)(=[O:31])[C:28]([CH3:30])=[CH2:29]>C1COCC1.CN(C1C=CN=CC=1)C.C([O-])(O)=O.[Na+]>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:27](=[O:31])[C:28]([CH3:30])=[CH2:29])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 13528Methacryloyl chloride2×HCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamine

Product 1

HCID 5328981N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]-2-methylacrylamideYield 32%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a stirred solution of 6-amino-4-[(3-bromophenyl)amino]quinazoline (J Med Chem, 1995;38:3482) (0.50 g, 1.59 mmol) in THF (20 mL) under nitrogen was added Et3N (excess, 1.0 mL), a catalytic amount of DMAP and methacryloyl chloride (1.1 mol eq., 1.75 mmol, 171 μL) dropwise. The reaction was stirred at 25° C. for 1.5 hours over which time two further amounts (50 μL) of methacryloyl chloride were added. The reaction was then diluted with saturated NaHCO3 and extracted with EtOAc. The combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on silica gel eluting with CH2Cl2/EtOAc (1:1) to MeOH/CH2Cl2/EtOAc (5:45:50). Recrystallization from EtOAc gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]-2-methylacrylamide (195 mg, 32%) as a cream powder, mp 244-245° C.

Workup

  1. additionwere added
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customchromatographed on silica gel eluting with CH2Cl2/EtOAc (1:1) to MeOH/CH2Cl2/EtOAc (5:45:50)
  6. customRecrystallization from EtOAc

Sources & evidence

ORD record
ord-a2b63b39ced44605ad60df61f6b9ab18
Source dataset
uspto-grants-2010_08
Patent number
US07786131B2

Reaction notes

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