Methacrylic Acid → HCID 18176145, Verbindung

HRID 507453Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 507453
[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

Komponenten

5

Edukt 3

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

Produkt 1

HCID 18176145HCID 18176145, VerbindungAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 7-amino-4-[(3-bromo-phenyl)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-dimethylamino-propyl)-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, mp (CH2Cl2/hexane) 255-259° C.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-68234d0f545f46a4858dd71363c7d102
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07786131B2

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