Acrylic Acid → 2-Propenamide, N-(4-((3-bromophenyl)amino)-7-quinazolinyl)-

HRID 394721Notes

Reaction equation

HRID 394721 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:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CO>[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:23])[CH:21]=[CH2:22])=[CH:3][CH:4]=3)[N:9]=[CH:8][N:7]=2)[CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 6581Acrylic AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 53280457-Amino-4-[(3-bromophenyl)amino]quinazoline

Product 1

HCID 98206442-Propenamide, N-(4-((3-bromophenyl)amino)-7-quinazolinyl)-Yield 27%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To an ice-cold solution of 0.158 g (0.5 mM) of 7-amino-4-(3-bromoanilino)-quinazoline [J Med Chem, 1995:3482] and 0.108 g of acrylic acid in 5.0 mL of dry dimethylformamide (DMF) was added 0.288 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (EDAC). After stirring for 5 minutes, the mixture became a solution, and the ice bath was removed. The reaction continued to stir at room temperature for 3 hours. The reaction was then poured into a mixture of ice and water and made basic with the addition of a saturated solution of sodium bicarbonate. This aqueous mixture was extracted three times with ethyl acetate, and the pooled extracts were dried over magnesium sulfate. The solution was filtered and concentrated in vacuo to afford a light yellow solid. The solid was dissolved in 100 mL of methanol, filtered, and concentrated in vacuo to approximately 10 mL. The solid which precipitated from solution was collected and dried in vacuo at 80° C. to give 50 mg of N-[4-(3-bromo-phenylamino)-quinazolin-7-yl]acrylamide, mp >265° C. Chemical ionization mass spectra: m/e 369.

Workup

  1. customthe ice bath was removed
  2. stirringto stir at room temperature for 3 hours
  3. additionThe reaction was then poured into a mixture of ice and water
  4. additionmade basic with the addition of a saturated solution of sodium bicarbonate
  5. extractionThis aqueous mixture was extracted three times with ethyl acetate
  6. dry with materialthe pooled extracts were dried over magnesium sulfate
  7. filtrationThe solution was filtered
  8. concentrationconcentrated in vacuo
  9. customto afford a light yellow solid
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo to approximately 10 mL
  12. customThe solid which precipitated from solution
  13. customwas collected
  14. customdried in vacuo at 80° C.

Sources & evidence

ORD record
ord-bf24e611fd8c4b079f2ff4859f73f6ab
Source dataset
uspto-grants-2003_08
Patent number
US06602863B1

Reaction notes

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