Triethylamine → 4-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester

https://huagongshe.com/reaction/2062187

Participants

Role	Name	HCID	Charge
Reactant	Triethylamine	HCID 8471	—
Reactant	4-Ethoxy-4-oxobut-2-enoic acid	HCID 41331	—
Reactant	Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate	HCID 151348	—
Reactant	6-[7-methyl-4-(1-piperazinyl)-1H-quinazolin-2-ylidene]-1-cyclohexa-2,4-dienone	HCID 136134616	—
Solvent	Water	HCID 962	—
Solvent	Dichloromethane	HCID 6344	—
Product	4-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester	HCID 136412249	91%

Reaction Steps

To 2-(7-methyl-4-piperazin-1-yl-quinazolin-2-yl)-phenol (787 mg, 2.46 mmol) in 8 mL of CH2Cl2 at room temperature was added sequentially but-2-enedioic acid monoethyl ester (531 mg, 3.69 mmol), triethylamine (686 μL, 4.92 mmol), BOP (1.63 g, 3.69 mmol). The reaction mixture was stirred for 20 min and diluted with water and CH2Cl2. The organic layer was separated and dried over Na2SO4, and the solvent was removed under reduced pressure to give an oil. The residue was subjected to purification by normal phase LC using 10-100% EtOAc-hexanes to give 4-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester (1.00 g, 91% yield). LC/MS: m/z 447.3 (M+H)+ at 2.93 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08283354B2
Source dataset	uspto-grants-2012_10
ORD ID	ord-589833afe5474c16a1b0f24670018a5f
Source note	uspto-grants-2012_10