6-BROMO-IMIDAZO[1,2-A]PYRIDINE-8-CARBOXYLIC ACID

To a stirred solution of 2-amino-5-bromonicotinic acid (5.0 g, 23.04 mmol) and sodium acetate (3.78 g, 46.1 mmol) in 100 ml_ of 60 percent ethanol in water, were added a refluxed solution of sodium acetate (3.78 g, 46.1 mmol) followed by 2-chloro-1 , 1 - dimethoxyethane (5.74 g, 46.1 mmol) in concentrated hydrochloric acid (1 .0 ml_) in water (6 ml_) and the reaction mass was refluxed for 2.5 h. The solvent was removed, residue obtained was diluted with cold water and pH adjusted to neutral (~7) with saturated sodium bicarbonate solution. The reaction mixture was extracted with ethyl acetate (2x100 ml_), washed with water (2x100 ml_) and brine (2x100 ml_) and dried over anhydrous sodium sulphate. The crude material obtained was purified by trituration using 2 percent ethyl acetate in petroleum ether. Yield: 4.8 g (86 percent); [0431] To a solution of Example 64a (240 mg, l.Ommol, ) and Example 64b (203 mg, 1.0 mmol) in 4 mL pyridine at 0C was added POCI3 (153 mg 1.0 mmol). The mixture was stirred at 0C for 1 hour. The mixture was quenched with water, extracted with EtOAc, organic layers were combined and concentrated. The residue was purified by Prep-HPLC (by Ultimate XB-C18, 50 x 250 mm, 10 mum, speed: 80 mL/min, eluent: H20/CH3CN = from 80/20 to 20/80 over 50 min) to afford Example 64c (140 mg, yield 33.0%) as a white solid. [0432] LC-MS [M+l] + = 427.9.The compound of example 23 (1.0 g, 4.15 mmol) was treated with (6-methoxypyridin-3- yl)boronic acid (0.761 g, 4.98 mmol) in the presence of [1 , 1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.102 g, 0.124 mmol) and sodium carbonate(0.879 g, 8.30 mmol) according to the procedure for the preparation of the compound of to afford the title compound. Yield: 0.3 g (27 %); 1H NMR (DMSO-d6, 300 MHz): delta 3.92 (s, 3H, OCH3), 6.98 (s, 1 H, Ar), 7.61 (s, 1 H, Ar), 8.04 (s, 1 H, Ar), 8.1 6 (dd, 1 H, J=2.4, 8.4Hz, Ar), 8.62 (d, 1 H, J=2.4 Hz, Ar); 8.92 (d, 1 H, J=1 .8 Hz, Ar), 9.06 (d, 1 H, J=2.4 Hz, Ar); MS (ES+): m/e 270 (M+1 ).The compound of example 23 (1 .0 g, 4.15 mmol) was treated with pyridin-3-ylboronic acid (0.510 g, 4.15 mmol) in the presence of [1 , 1 '-bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) complex with dichloromethane (0.102 g, 0.124 mmol) and sodium carbonate(0.829 g, 8.30 mmol) according to the procedure for the preparation of the compound of to afford the title compound. Yield: 0.4 g (40.3 %); 1H NMR (DMSO-d6, 300 MHz): delta 7.54 (q, 1 H, J=4.8 Hz, Ar), 7.68-7.72 (m, 2H, Ar), 8.04 (s, 1H, Ar), 8.53-8.65 (m, 2H, Ar), 8.99 (d, 1H, J=1.8 Hz, Ar); 9.29 (d, 1H, J=1.8 Hz, Ar); MS (ES+): m/e 240 (M+1).

Molecular Weight:241.04
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:239.95344
Monoisotopic Mass:239.95344
Topological Polar Surface Area:54.6
Heavy Atom Count:13
Complexity:224
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes