Acrylic Acid → pd 168393

HRID 507449Notes

Reaction equation

HRID 507449 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.[C:20](O)(=[O:23])[CH:21]=[CH2:22].Cl.CN(C)CCCN=C=NCC>CN(C=O)C>[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:20](=[O:23])[CH:21]=[CH2:22])[CH:3]=3)[N:8]=[CH:7][N:6]=2)[CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 6581Acrylic Acid2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5328042N4-(3-Bromophenyl)quinazoline-4,6-diamine

Product 1

HCID 4708pd 168393Yield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-amino-4-[(3-bromophenyl)amino]-quinazoline (2.0 g, 6.35 mmol) in dry DMF (20 mL) under N2 was added acrylic acid (12.7 mmol, 0.87 mL). The resulting solution was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI·HCl) (7.62 mmol, 1.46 g) was added. The reaction was stirred at 0° C. for 15 minutes and then allowed to warm to room temperature and stirred for a further 2 hours, after which additional acrylic acid (0.30 mL) and EDCI·HCL (0.30 g) were added. After a further 2 hours, the reaction was complete by tlc, solvent was removed under reduced pressure, and the resulting residue diluted with saturated NaHCO3 and repeatedly extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. Column chromatography on grade III alumina eluting with EtOAc/MeOH (95:5) followed by recrystallization from EtOAc/hexane gave a spongy white solid, which upon several hours under high vacuum gave N-[4-[(3-bromophenyl)amino]quinazolin-6-yl]acrylamide (1.06 g, 45%) as a cream powder, mp 258-261° C.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 2 hours
  3. waitAfter a further 2 hours
  4. customwas removed under reduced pressure
  5. additionthe resulting residue diluted with saturated NaHCO3
  6. extractionrepeatedly extracted with EtOAc
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customColumn chromatography on grade III alumina eluting with EtOAc/MeOH (95:5) followed by recrystallization from EtOAc/hexane
  11. customgave a spongy white solid, which upon several hours under high vacuum

Sources & evidence

ORD record
ord-4094429492154f2dbcefff644399bdf5
Source dataset
uspto-grants-2010_08
Patent number
US07786131B2

Reaction notes

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