Pyrazolo[1,5-a]pyridine-3-carboxylic acid, 5-bromo-, ethyl ester

Compound 64.3. Ethyl 5-bromopyrazolo[l, 5-a]pyridine-3-carboxylate. Into a 250-mL three neck round-bottom flask, was placed a solution of l-amino-4-bromopyridin-l- ium iodide (compound 64.2, 15 g, -50percent purity, 24.9 mmol) in N.N-dimethylformamide (80 mL). Potassium carbonate (10.6 g, 76.7 mmol) was added portion-wise followed by the addition of ethyl propiolate (1 1.7 mL, 1 15 mmol) drop-wise over 10 min. The resulting mixture was stirred overnight at room temperature, then diluted with EtOAc (300 mL) and water (100 mL). The solids were removed by filtration and the organic layer was washed with brine (3 x 50 mL), dried (NaCompound 64.3. Ethyl 5-bromopyrazolo[l, 5-]pyridine-3-carboxylate. To a stirred solution of 4-bromopyridine (64.0 g, 40.5 mmol) in DME (200 mL) at 0 °0 was added O-(mesitylsulfonyl)hydroxylamine (80.0 g, 37.1 mmol) portion wise over a period of 20 mm. The resultant reaction mixture was allowed to warm to room temperature and maintained at 40°C for 16 h. The reaction mixture was cooled toO °0, diluted with DME (200 mL), K2003 (128 g, 92.7 mmol) followed by ethyl propiolate (43.07 mL, 42.5 mmol) were added and the resulting reaction mixture was stirred at rt for 6 h. The reaction mixture was poured on to ice-cold water, extracted with ethyl acetate (2 x 1000 mL). The ethyl acetate layer was washed with water, brine, dried over anhyd. Na2SO4 and concentrated. The crude compound was purified by column chromatography over silica gel (100—200 mesh) using a solvent gradient mixture of 7percent ethyl acetate in pet-ether to afford 3.5 g (3percent) of ethyl 5-bromopyrazolo[1 , 5-a]pyridine-3-carboxylate 94-1 as a light brown solid. ESI-LC/MS: m/z269.2 (M+H) & 271.2 [(M+2)+H]; R = 3.46 mm [Agilent [C with Ion trap Detector; Symmetry 018, 3.5 pm, 4.6 X 75mm column; gradient of 50:50 H20 (0.1percent H000H): CH3CN (0.1percent H000H) to 10:90 H20 (0.1percent H000H):CH3CN (0.1percent H000H) in 4.0 mm and hold for 3.0 mm with flow rate of 1.0 mL/min].

Molecular Weight:269.09
XLogP3:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:267.98474
Monoisotopic Mass:267.98474
Topological Polar Surface Area:43.6
Heavy Atom Count:15
Complexity:250
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes