3-BROMO-2-CHLORO-6-PICOLINE

Yellow low melting solid or liquid

General procedure: Method A: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 3-bromo-2-fluoropyridine (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DMAP (2.5 mmol). The tube was purged with argon. Then DMF (10V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a preheated oil bath at 120 0C for 8 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding pyridobenzoxazepinone. Method B: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 3-bromo-2-chloropyridine (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DBU (2.5 mmol). The tube was purged with argon. Then DMF (10 V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a pre heated oil bath at 135 0C for 12 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding pyridobenzoxazepinone.General procedure: Method A: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 3-bromo-2-fluoropyridine (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DMAP (2.5 mmol). The tube was purged with argon. Then DMF (10V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a preheated oil bath at 120 0C for 8 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding pyridobenzoxazepinone. Method B: A sealed tube equipped with a magnetic stir bar was charged with the corresponding 3-bromo-2-chloropyridine (1 mmol), amino phenol (1 mmol), Pd(OAc)2 (5 mol%), xantphos (5 mol%) and DBU (2.5 mmol). The tube was purged with argon. Then DMF (10 V) was added followed by the addition of Co2(CO)8 (0.25 mmol). The tube was closed with seal plug instantly. The reaction tube was placed in a pre heated oil bath at 135 0C for 12 h. On completion, the reaction mixture was cooled to room temperature, added water and ethyl acetate (1:1). Precipitated solid was filtered through a Celite bed. The bed was washed thoroughly with ethyl acetate. Organic layer was separated. Aqueous layer extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous sodium sulphate. Organic layer was concentrated under reduced pressure and purified by flash column chromatography on silica gel (230-400 mesh) with ethyl acetate and petroleum ether as eluent to afford the corresponding pyridobenzoxazepinone.To a solution of To a solution of Example 12Preparation of lambda/-[2-amino-1-(phenylmethyl)ethyl1-6-chloro-5-(1-methyl-1 H-pyrazol- 5-yl)-2-pyridinecarboxamidea) S-bromo^-chloro-beta-methylpyridine N-oxideTo a solution of S-bromo^-chloro-beta-methylpyridine (1 g, 4.84 mmol) and urea hydrogen peroxide (91 1 mg, 9.69 mmol) in DCM (24 ml.) at 0 0C was added trifluoroacetic anhydride (1.4 ml_, 9.69 mmol). After warming to 25 0C over 12h, the solution was partitioned between H2O-DCM. The aqueous phase was washed several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 1% MeOH in DCM) yielding the title compound (1.1 g, quant.) as a white solid: LCMS (ES) m/z = 223 (M+H)+.b) N-[2-aminoTo a solution of

Molecular Weight:206.47
XLogP3:2.9
Hydrogen Bond Acceptor Count:1
Exact Mass:204.92939
Monoisotopic Mass:204.92939
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes