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

HRID 394742Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 394742
[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

Komponenten

7

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-c633b63777fe4694b52b9e46f7db32b9
Quelldatensatz
uspto-grants-2003_08
Patentnummer
US06602863B1

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