6-Chloro-4-methoxy-3-pyridinecarboxylic acid

To a solution of the intermediate of step 2 (2.94 g, 14.6 mmol) in a mixture of MeOH (30 mL), THF (30 mL) and HStep 1[00163j To a solution of 4, 6-dichioronicotinic acid (4 g, 20.8 mmol) in methanol (8mL) and tetrahydrofuran (16 mL) was added lithium hydroxide mono-hydrate (2.62 g, 62.5 mmol) and the reaction was stirred at room temperature for 1 hour. The reaction was concentrated under reduced pressure and 12 mL of water was added, the solution was cooled to 0 °C and 1 N hydrochloric acid (aqueous) was added while the solution was agitated resulting in a precipitate. Gradual addition of the acid was continued until the pHmeasured (litmus paper) to be 4. The suspension was then filtered and the solid collected and triturated with diethyl ether for 1 hour. The solid was filtered, dried and collected yielding Intermediate 6 (2.84 g, 73percent). ‘H NMR (400MHz, DMSO-d6) ö 13.23 (br. s., 1H), 8.54 (s, 1H), 7.32 (s, 1H), 3.94 (s, 3H). LC retention time 0.55 mm [J]. MS(Ej m/z: 188 (MHj.General procedure: The corresponding onium triflate precursors of radiolabeled active esters, [ F]8 and [ F]9, were prepared by the reaction of 2, 3, 5, 6-tetrafluorophenyl 6-chloro-2- or -4- methoxynicotinates (13 and 14, respectively) with Me3N followed by anion metathesis usingTMSOTf (Fig. 3). 13 and 14 were synthesized from the appropriate chloroanhydrides [obtained by the treatment of 6-chloro-2- or -4-methoxynicotinic acids (17 and 18, respectively) with oxalyl chloride in the presence of DMF traces] and 2, 3, 5, 6- tetrafluorophenol using Et3N as a base. 17 and 18 were prepared from 2, 6- and 2, 4- dichloronicotinic acids, respectively, by the reaction with MeONa, generated in situ from MeOH and NaH.[16]Similarly, the precursor of 2-EtO-6-[18F]FNic-OTfp (16) was prepared.To a stirred solution of 314 methyl 4, 6-dichloronicotinate (20.0 g, 97.09 mmol, 1.0 eq), in 165 THF (80 mL) and 30 MeOH (40 mL) was added LiOH.H2O (12.22 g, 291.29 mmol, 3.0 eq) at rt. The resulting mixture was stirred at the same temperature for 12 h. The reaction mixture was concentrated and diluted with water (100 mL), followed by dropwise addition of 1N 31 HCl (50 mL), white precipitate formed was collected by filtered and dried under vacuum to afford the desired compound, 315

Used for preparation of benzimidazolylazabicyclooctylethylpiperidines as Ccr5 antagonists for the treatment of HIV infection.

Molecular Weight:187.58
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:187.0036207
Monoisotopic Mass:187.0036207
Topological Polar Surface Area:59.4
Heavy Atom Count:12
Complexity:176
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes