3-Bromoisonicotinic acid

3-Bromopyridine30 (164mg, 1.0 mmol) was added to LiNPrA mixture of 3.98 g of the acid obtained in the previous step (20 mmol, 1 eq.) in 50 ml of methanol is reflux heated in the presence of 4 ml of concentrated sulfuric acid. The mixture is allowed to return to ambient temperature and extracted 3 times with ethyl acetate. The organic phase is dried on NaReference 3-Bromoisonicotinic acid (3.02 g , 15 mmol) was dissolved in dichloromethane (20 mL). Oxalyl chloride (9.53 g, 75 mmol) was added. After gas evolution had ceased (~1 hour), the solvent was removed in vacuo and the residue redissolved in dichloromethane. N, O-dimethylhydroxylamine hydrochloride (2.94 g, 30 mmol) was added followed by triethylamine (4.55 g, 45 mmol) and the reaction was stirred for one hour at room temperature. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and evaporated to yield 3-bromo-N-methoxy-N-methylisonicotinamide, 1.2 g of which was dissolved in THF (10 mL) and cooled to 00C. Methyl magnesium bromide (4.92 ml, 9.84 mmol) was added and the reaction was allowed to warm to room temperature and stirred for two hours before being quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was dried over MgSO4 and evaporated. The residue was purified by flash column EPO General procedure: To a solution under argon of the appropriate acid (1 equiv.) in anhydrous benzene (3 mL/1 mmol of acid) was added oxalyl chloride (1.5 equiv.), followed by N, N-dimethylformamide (2 drops). When gas evolution had ceased (30 min.), the reaction mixture was concentrated under vacuum to afford the crude acyl chloride, which was used without further purification. Triethylamine (3 equiv.) was added to a solution under argon of the appropriate amine (1 equiv.) in anhydrous CH2Cl2 (2 mL / 1 mmol of acid). The acyl chloride (1 equiv.) in anhydrous CH2Cl2 (2 mL / 1 mmol of acid) was added dropwise to this mixture. After 60 min, the reaction mixture was concentrated and the crude product was directly purified by chromatography on silica gel to yield the expected amide.The following compounds, for example, are illustrative: ... 2-chloro-6-methylnicotinic acid, 4-fluoronicotinic acid, 4-chloronicotinic acid, 3-fluoroisonicotinic acid, General procedure: To a solution of Intermediate 7 (110 mg, 0.37 mmol), 3-methoxybenzene-1, 2- diamine (50 mg, 0.34 mmol) and DIPEA (0.2 mL, 1 mmol) in DMF (2 mL) was added HATU (160 mg, 0.41 mmol). The reaction mixture was stirred at r.t. for 48 h, then partitioned between DCM and water. The organic phase was separated, then dried and concentrated in vacuo. The crude residue was purified by flash column chromatography (0-100% EtOAc/hexanes) to give the title compound (28.7 mg, 20%) as a white solid. LCMS (Method 5): [M+H]+ m/z 415, RT 1.31 minutes.General procedure: To a solution of Intermediate 7 (110 mg, 0.37 mmol), 3-methoxybenzene-1, 2- diamine (50 mg, 0.34 mmol) and DIPEA (0.2 mL, 1 mmol) in DMF (2 mL) was added HATU (160 mg, 0.41 mmol). The reaction mixture was stirred at r.t. for 48 h, then partitioned between DCM and water. The organic phase was separated, then dried and concentrated in vacuo. The crude residue was purified by flash column chromatography (0-100% EtOAc/hexanes) to give the title compound (28.7 mg, 20%) as a white solid. LCMS (Method 5): [M+H]+ m/z 415, RT 1.31 minutes.General procedure: To a solution of Intermediate 7 (110 mg, 0.37 mmol), 3-methoxybenzene-1, 2- diamine (50 mg, 0.34 mmol) and DIPEA (0.2 mL, 1 mmol) in DMF (2 mL) was added HATU (160 mg, 0.41 mmol). The reaction mixture was stirred at r.t. for 48 h, then partitioned between DCM and water. The organic phase was separated, then dried and concentrated in vacuo. The crude residue was purified by flash column chromatography (0-100% EtOAc/hexanes) to give the title compound (28.7 mg, 20%) as a white solid. LCMS (Method 5): [M+H]+ m/z 415, RT 1.31 minutes.Compound 40a. To a solution of

Molecular Weight:202.01
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:200.94254
Monoisotopic Mass:200.94254
Topological Polar Surface Area:50.2
Heavy Atom Count:10
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes