6-BROMO-IMIDAZO[1,2-A]PYRIDIN-8-AMINE

To a soln of [BROMOACETALDEHYDE] diethyl acetal (2.37 mL, 15.4 [MMOL)] in [DIOXANE/H20] (2: 1/15 mL) at rt was added conc. [HCI] (0.3 mL) and the mixture was refluxed for 30 min. The mixture was cooled to rt whereupon [NAHCO3] (2.6 g, 30.8 [MMOL)] was carefully added followed by dropwise addition of diamino derivative (1.5 g, 7.7 [MMOL)] in [DIOXANE/H20] (2: [1/15] mL). The resultant mixture was stirred at reflux for 14 h and was cooled to rt. The mixture was diluted with 1 M [NAOH] (30 mL) and was extracted with [CH2CI2] (3 x 35 mL). The organic layers were combined, washed with brine [(1] x 20 mL), dried [(NA2SO4), ] filtered and concentrated under reduced pressure to afford 1.5 g (92percent) of the desired compound [[M +] H = 214. [0].][0264] To a stuffed solution of compound I (50 g; 0.26 mol; 1 eq) in ethanol (2 L) was added sodium bicarbonate (46 g; 0.53 mol; 2 eq) and chloroacetaldehyde solution (—50percent aqueous solution, 86 mL; 0.66 mol; 2.5 eq) drop wise and the resulting mixture was heated at reflux for 17 h. The mixture was then evaporated to dryness and the pH was adjusted to 7 using ice-cold saturated aqueous NaHCO3 solution and solid NaHCO3. The organic components were extracted from the aqueous layer with ethyl acetate (3 x 1000 mL) and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and the solvent was removed in vacuo to obtain a dry residue which was purified by silica gel (230-400 mesh) column chromatography using 10-50percent ethyl acetate/hexanes as the eluent to afford the title compound (40 g, 71percent) as a brown solid. 1H NMR (DMSO-d6) ö 8.04 (s, 1H), 7.77 (s, 1H), 7.44 (s, 1H), 6.31 (s, 1H), 5.99 (s, 2H). LCMS: m/z = 212.0 [M+j, 214.0 [M+21, RT = 2.55 minutes, (Program P1, Column V).To a stirred solution of 5-bromopyridine-2, 3-diamine (278 g, 1478 mmol) in isopropanol (2.2 L) at rt was added chloroacetaldehyde (255 g, 1626 mmol) in one portion. After stirring in an nitrogen atmosphere under reflux overnight, the mixture was stirred for an additional 60 min at rt. The suspension was filtered, and the remaining solid was washed with isopropanol and dried in vaccuo at 50° C. Redissolution in methanol and evaporation yielded 6-bromoimidazo[1, 2-a]pyridin-8-amine as a brown solid (124 g, 40 3/4):

Molecular Weight:212.05
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:210.97451
Monoisotopic Mass:210.97451
Topological Polar Surface Area:43.3
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes