Methacrylic Acid → HCID 18176145, compound

HRID 1698943Notes

Reaction equation

HRID 1698943 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:20](O)(=[O:24])[C:21]([CH3:23])=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[Br:19][C:15]1[CH:14]=[C:13]([NH:12][C:6]2[C:5]3[C:10](=[CH:11][C:2]([NH:1][C:20](=[O:24])[C:21]([CH3:23])=[CH2:22])=[CH:3][CH:4]=3)[N:9]=[CH:8][N:7]=2)[CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 4093Methacrylic Acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 53280457-Amino-4-[(3-bromophenyl)amino]quinazoline

Product 1

HCID 18176145HCID 18176145, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 7-amino-4-[(3-bromophenyl)amino]quinazoline (J Med Chem, 1995;38:3482) (150 mg, 0.48 mmol) in dry DMF (20 mL) was added methacrylic acid (200 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI.HCl) (2.5 mol, 228 mg), the reaction mixture was stirred overnight then further amounts of EDCI.HCl (230 mg) and methacrylic acid (200 mg) were added. After a further 2 days stirring the solvent was removed under vacuum and the residue diluted with saturated NaHCO3, extracted with ethyl acetate (EtOAc) and then the combined organic extracts were dried over anhydrous Na2SO4, concentrated under reduced pressure and chromatographed on silica gel eluting with MeOH/CH2Cl2/EtOAc (5:45:50) to MeOH/CH2Cl2/EtOAc (10:40:50) to give N-[4-[(3-bromophenyl)amino]quinazolin-7-yl]-2-methyl-acrylamide (43 mg, 24%) as a pale brown solid, np (CH2Cl2/hexane) 255-259° C.

Workup

  1. stirringAfter a further 2 days stirring the solvent
  2. customwas removed under vacuum
  3. additionthe residue diluted with saturated NaHCO3
  4. extractionextracted with ethyl acetate (EtOAc)
  5. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customchromatographed on silica gel eluting with MeOH/CH2Cl2/EtOAc (5:45:50) to MeOH/CH2Cl2/EtOAc (10:40:50)

Sources & evidence

ORD record
ord-b27263381c2c4b7da84bd2b79565d89f
Source dataset
uspto-grants-2002_02
Patent number
US06344459B1

Reaction notes

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