ChemInform Abstract: Syntheses of 4‐(Indole‐3‐yl)quinazolines — A New Class of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.

Abstract

The syntheses of the (indolyl)quinazolines (VIII) and (XIII) proceed via two key steps. The first one involves the intramolecular cyclization of the cinnamic acid esters (IV). The ring closure of ester (IVb) does not occur regiospecifically but affords a mixture of two indole carboxylic esters. The second key step is based on a chemoselective and regioselective hetarylation reaction: indolyl-magnesium compounds are reacted with chloroquinazolines like (VII) to yield the targets (VIII) and (XIII). These compounds are relatively potent inhibitors of EGFR-TK. In addition, compound (XIII) can also be viewed as HER-2-tyrosine kinase inhibitor. Moreover, the new class shows remarkable strong fluorescence properties. -(LUETH*, A.; LOEWE, W.; Eur.

Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5

“…Compound 1 was synthesized as outlined in Scheme : Following a literature procedure, anthranilic acid 2 was converted to the corresponding 4-chloro-6,7-dimethoxyquinazoline. , Subsequent Suzuki reaction, cleavage of the Boc protecting group, and hydrogenation of the double bond furnished piperidine derivative 4 . Amide formation with 4-(trifluoromethoxy)­benzoic acid gave rise to compound 1 .…”

“…The syntheses and analytical data for all other compounds (2−40, 42) are described in the Supporting Information. 1 H NMR purities were determined to be Step 1: To a solution of 4-chloro-6,7-dimethoxyquinazoline (0.8 g, 3.6 mmol, prepared according to literature procedure 12,13 ) in 10 mL of 1,4dioxane/water (v/v = 5:1) were added tert-butyl 4-(4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate (1.70 g, 5.3 mmol), sodium carbonate (1.50 g, 14.2 mmol), and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) chloride (0.3 g, 0.4 mmol). The resulting mixture was stirred at 100 °C for 4 h under nitrogen atmosphere.…”