dimethyl4-chloropyridine-2,6-dicarboxylate

White solid

PClA few drops of anhydrous dimethylformamide were added to a solution of chelidamic acid 24 (17 g, 93 mmol) in thionyl chloride (95 mL). This solution was heated at 100° C. for 48 h. The thionyl chloride was removed under reduced pressure. Dichloromethane (50 mL) was added to this residue and the mixture was cooled to 0° C. Anhydrous methanol (40 mL) was added dropwise to this mixture in the space of 10 min and the mixture was heated at room temperature and then was stirred overnight. The solvents were removed under reduced pressure and saturated solution of sodium bicarbonate (100 mL) was added to this residue. The mixture was filtered and the filtrate was extracted with dichloromethane (3×50 mL), the organic phases were combined, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give a white solid identified as compound 25. The product was sufficiently pure to be used in the rest of the synthesis without additional purification (13.3 g, 63percent). M.p.: 141-142° C. Anhydrous DMF (27.6 mL, 358 mmol) was added slowly to a suspension of chelidamic acid monohydrate (1) (36.0 g, 179 mmol) in SOCl2 (230 mL, 3.17 mol) (caution: exothermic reaction and vigorous gas evolution). After 1 h of stirring at room temperature, the suspension was slowly heated to reflux (oil bath temperature 95 °C) and stirred at this temperature for 22 h (caution: vigorous gas evolution). During this time the suspension turned into a pale yellow solution. The excess SOCl2 was distilled off under reduced pressure. To the cooled (ice bath) residual orange-red solid, MeOH (500 mL) was added slowly (caution: exothermic reaction and vigorous gas evolution). The resulting suspension was heated to reflux (oil bath temperature 70 °C)and MeOH was added until all of the solid was dissolved. Upon slowly cooling to room temperature, colorless needles formed. The suspension was cooled with an ice-water bath and the needles were collected by filtration and washed with cold MeOH to obtain chloro diester 2(35.6 g, 87percent); mp 139–140 °C.1H NMR (500 MHz, CDCl3): δ = 8.28 (s, 2 H, ArH), 4.02 (s, 6 H, Me).13C NMR (125 MHz, CDCl3): δ = 163.9 (C=O), 149.3 (CAr meta to Cl), 146.6 (CArCl), 128.1 (CArH), 53.3 (CH3).MS (ESI): m/z = 480.9 [2 M + Na]+, 251.9 [M + Na]+, 229.9 [M + H]+.HRMS (EI, 70 eV): m/z [M]+• calcd for C9H8ClNO4+•: 229.01364; found:229.01373.Anal. Calcd for C9H8ClNO4: C, 47.08; H, 3.51; N, 6.10. Found: C, 47.18;H, 3.51; N, 6.07.A few drops of dimethylformamide were added to a solution of chelidamic acid 9 (17 g, 93 mmol) in thionyl chloride (95 mL). This solution was heated at 100° C. for 48 hours. The thionyl chloride was moved under reduced pressure. Dichloromethane (50 mL) was added to this residue, and the mixture was cooled to 0° C. Anhydrous methanol (40 mL) was added dropwise to this mixture over a period of 10 minutes, and the mixture was allowed to warm to room temperature over night. The solvents were removed under reduced pressure and saturated sodium bicarbonate solution (100 mL) was added to this residue. The mixture was filtered and the filtrate was extracted with dichloromethane (3×50 mL), the organic phases were combined, dried over sodium sulfate, filtered and evaporated under reduced pressure to give a white solid identified as compound 10. The product was sufficiently pure to be used in the rest of the synthesis without further purification (13.3 g, 63percent).

Molecular Weight:229.62
XLogP3:1.9
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:229.0141854
Monoisotopic Mass:229.0141854
Topological Polar Surface Area:65.5
Heavy Atom Count:15
Complexity:235
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes