4-Methylmorpholine → 4-(4-Methyl-piperazin-1-yl)-but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide

Isobutyl chloroformate (0.905 g, 6.6 mmol) and N-methylmorpholine (1.550 g, 15.3 mmol) were added to an ice cold solution of 1.900 g (10.71 mmol) of 4-(4-methyl-piperazin-1-yl)-but-2-ynoic acid in l50 mL of tetrahydrofuran under nitrogen. After stirring for 30 min, a solution of 1.500 g of N-(3-bromophenyl)-4,6-quinazolindiamine in 12 mL of pyridine was added and the mixture was stirred for 2 hr at 0° C. The reaction was then quenched with ice water, then it was poured into saturated sodium bicarbonate, and the product was extracted with ethyl acetate. Chromatography of the extract on silica gel, eluting with methanol/ethyl acetate (30:70), gave 0.590 g of 4-(4-methyl-piperazin-1-yl) -but-2-ynoic acid [4-(3-bromo-phenylamino)-quinazolin-6-yl]-amide: mass spectrum (m/e): M+H 479.

1. stirringthe mixture was stirred for 2 hr at 0° C
2. customThe reaction was then quenched with ice water
3. additionit was poured into saturated sodium bicarbonate
4. extractionthe product was extracted with ethyl acetate
5. extractionChromatography of the extract on silica gel
6. washeluting with methanol/ethyl acetate (30:70)

ORD-Eintrag

ord-3c0727e8d3d64f29a7ecbf40bedb6d78

Quelldatensatz

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06251912B1