Methyl 6-bromo-2-pyridinecarboxylate

White to off-white solid

Compound V: 6-Bromopyridine-2-carboxylic acid methyl ester 6-Bromopyridine-2-carboxylic acid (6. 000g) was heated in refluxing methanol (180mL) containing conc. sulphuric acid (2mL) for 4 hrs. The reaction mixture was then cooled to ~0°C and conc. ammonia (4.8mL) was added. The resulting solution was evaporated to give a white residue. This white solid was partitioned between brine and dichloromethane (100/100mL). After thorough shaking the organic layer was dried (magnesium sulphate) and evaporated to give a white solid. (6. 300g, 98percent). 'H NMR (400MHz, CDCI3) 4.00 (3H, s), 7.66-7. 74 (2H, m), 8.07-8. 13 (1 H, m).To the solution of 6-bromopicolinic acid (20g, 9.90 mmol) in methanol (lOOmL) was added SOC12 (36.8 mL, 49.Smmol) at 0°C, stined at 70°C for 2h. The reaction was monitored by TLC (20percent EtOAc in Hexane). Then the solvent was distilled out, and the reaction mixture wasbasified with saturated NaHCO3 solutio and was filtered. The solid was dried under vacuum to give title compound. (20g, 92.6percent)General procedure: The reaction vessel was charged with the heteroaromatic malononitrile (1.0 equiv, prepared according to ref. 6) and the specified solvent (1 mL per0.12 mmol). It was stirred at r.t. and 4 Å molecular sieve was added. Anhydrous m-CPBA (1.5 equiv) solution was prepared by dissolving in the specified solvent (1 mL per 0.22 mmol) and drying over molecular sieves (4 Å) for 10 min. This solution was added to the reaction mixture which was subsequently stirred for 10 min. After adding the nucleophile, the reaction mixture was stirred at r.t. The reaction was finally quenched with aq sodium thiosulfate solution and extracted with CH2Cl2. The combined organics were washed twice with saturated aqueous solution of NaHCO3 and brine, dried over Na2SO4 and concentrated in vacuo. Further purification was carried out by preparative HPLC.Y Preparation of Examples 30 and 31; Methyl ester 22 was prepared in a manner similar to that of ethyl ester 5 of Example 173 in U. S. Serial No. 10/358, 898, as follows. Preparation of methyl ester 25; Step 1:; A solution of 6-bromopicolinic acid (20.0 g, 99 mmol) in DMF (60 mL) was treated with K2C03 (16.6 g, 120 mmol) followed by Mel (6.8 mL, 109 mmol). After 18 h, the reaction mixture was diluted with H2O and extracted with EtOAc (2x). The combined organic extracts were washed with H20 (3x), brine, dried over MgS04 and concentrated in vacuo to provide bromide 22 (16.9 g, 79percent) as an off-white solid.To a solution of 6-bromopicolinic acid (2.5 g) in MeOH (100 mL) was added concentrated H

Molecular Weight:216.03
XLogP3:2.1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:214.95819
Monoisotopic Mass:214.95819
Topological Polar Surface Area:39.2
Heavy Atom Count:11
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes