3-Bromo-1,5-naphthyridine

3-Bromo-1, 5-naphthyridine (5) To a stirring solutionof compound 4 (2.7 g, 20.76 mmol) and NaOAc(3.41 g, 41.52 mmol) in 10 mL glacial AcOH at 85°C was added a solution of BrTo a stirred mixture of 1, 5-naphthyridine (C-1) (50.0 g, 384 mmol, 1.0 eq) and sodium acetate(62.9 g, 768 mmol, 2.0 eq) in acetic acid (300 mL) at 80 °C, a solution of bromine (67.5 g, 422 mmol, 1.1 eq) in acetic acid (80 mL) was added dropwise while keeping the reaction temperature at 80 °C to 90 °C. After stirring for 2 h at 80 °C, the reaction was complete based on TLC analysis. The resulting mixture was cooled to RT and then filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (0-30percent ethyl acetate-petroether) to afford the desired product 3-bromo-l, 5-naphthyridine (C-2) (36.5 g, 45 percent yield ) as a pale yellow solid. Example la: Synthesis of 3-bromo-l, 5-naphthyridine (C-2) [00305] To a stirred mixture of 1, 5-naphthyridine (C-1) (50.0 g, 384 mmol, 1.0 eq) and sodium acetate(62.9 g, 768 mmol, 2.0 eq) in acetic acid (300 mL) at 80 °C, a solution of bromine (67.5 g, 422 mmol, 1.1 eq) in acetic acid (80 mL) was added dropwise while keeping the reaction temperature at 80 °C to 90 °C. After stirring for 2 h at 80 °C, the reaction was complete based on TLC analysis. The resulting mixture was cooled to RT and then filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (0-30percent ethyl acetate-petroether) to afford the desired product 3-bromo-l, 5-naphthyridine (C-2) (36.5 g, 45 percent yield ) as a pale yellow solid. A solution of ethyl 2, 3-dihydro-lH-isoindole-4-carboxylate hydrochloride (80 mg, 0.35 mmol), 3-bromo-l, 5-naphthyridine (144 mg, 0.69 mmol), Pd2(dba)3-chloroform adduct (18.2 mg, 0.018 mmol), XantPhos (20.3 mg, 0.04 mmol), and cesium carbonate (344 mg, 1.06 mmol) in toluene (5 mL) stirred for 16 h at 100 C. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2x20 mL of dichloromethane, and the combined organic phases were washed with 1x10 mL of brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 20:1 dichloromethane/methanol) to afford ethyl 2-(l, 5-naphthyridin-3-yl)-2, 3-dihydro-lH-isoindole-4-carboxylate (110 mg, 98%) as a red solid. MS: (ESI, m/z): 320[M+H]+.

Molecular Weight:209.04
XLogP3:1.9
Hydrogen Bond Acceptor Count:2
Exact Mass:207.96361
Monoisotopic Mass:207.96361
Topological Polar Surface Area:25.8
Heavy Atom Count:11
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes