Methyl 1-(2,3-dihydroxypropyl)-1,4-dihydro-4-oxo-3-(phenylmethoxy)-2-pyridinecarboxylate

A reactor was charged with 1-(2, 3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1 , 4- dihydro-2-pyridinecarboxylic acid 6 (4.302 kg, 13.47 mol) followed by charging withNaHCOAreactor was charged with 1-(2, 3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1, 4-dihydro-2-pyridinecarboxylic acid 6 (4.302 kg, 13.47 mol) followed by charging with NaHCOTo a slurry of 576 g of compound 6(1.0 eq.: 5.8percent of Hf) Synthesis of methyl 1 -(2, 3-dihydroxypropyl)-4-oxo-3- [(phenylmethyl)oxy]-1 , 4-dihydro-2-pyridinecarboxy- late (compound P-7). To a slurry of 576 g of compound P-6 (1.0 eq.: 5.8percent of H20 was contained) in 2.88 E ofNMP were added 431 g of NaHCO3 (3.0 eq.) and 160 mE of methyl iodide (1.5 eq.) and the mixture was stirred at room temperature for 4 h. Afier cooling to 5° C. 1.71 E of 2N HC1 and 1.15 E of 20percent NaClaq were added to the mixture at less than 10° C. to give crystal of compound 7. Filtration, washing with 1.73 E of H20 and drying provided 507 g of compound P-7 (89percent yield) as a solid. ‘H NMR (300 MHz, DMSO-d5) ö 7.59 (d, J=7.5 Hz, 1H), 7.40-7.28 (m, 5H), 6.28 (d, J=7.5 Hz, 1H), 5.21 (d, J=5.4 Hz, 1H), 5.12 (d, J=10.8 Hz, 1H), 5.07 (d, J=10.8 Hz, 1H), 4.83 (t, J=5.7 Hz, 1H), 3.97 (dd, J=2.4, 14.1 Hz, 1H), 3.79 (s, 3H), 3.70 (dd, J=9.0, 14.4 Hz, 1H), 3.65-3.50 (m, 1H), 3.40-3.28 (m, 1H), 3.26-3.14 (m, 1H).To a slurry of 576 g of compound 6(1.0 eq.: 5.8percent of HStep E - Synthesis of Intermediate Compound A Into a 2-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen. This was followed by the addition of 3-(benzyloxy)-l-(2, 3- dihydroxypropyl)-4-oxo-l, 4-dihydropyridine-2-carboxylic acid If (200 g, 626.35 mmol, 1.00 equiv), NMP (1000 mL), sodium bicarbonate (158 g, 1.88 mol, 3.00 equiv), CHA reactor was charged with 1-(2, 3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1 , 4- dihydro-2-pyridinecarboxylic acid 6 (4.302 kg, 13.47 mol) followed by charging withNaHCOAreactor was charged with 1-(2, 3-dihydroxypropyl)-4-oxo-3-[(phenylmethyl)oxy]-1, 4-dihydro-2-pyridinecarboxylic acid 6 (4.302 kg, 13.47 mol) followed by charging with NaHCO(4) 10 g of Intermediate 4, 7.9 g of sodium hydrogencarbonate and 6.7 g of methyl iodide were added to 20 mL of N-methylpyrrolidone, and the mixture was stirred at room temperature for 5 hours, and the reaction was completed.Under ice water bath, dilute hydrochloric acid adjusts the system pH=4, adding a lot of water, a yellow solid precipitates, Filtered, washed, dried, Yield 9.9 g of a white solid, intermediate 5, yield: 95percent.To a slurry of 576 g of compound 6(1.0 eq.: 5.8percent of Hf) Synthesis of methyl 1 -(2, 3-dihydroxypropyl)-4-oxo-3- [(phenylmethyl)oxy]-1 , 4-dihydro-2-pyridinecarboxy- late (compound P-7). To a slurry of 576 g of compound P-6 (1.0 eq.: 5.8percent of H20 was contained) in 2.88 E ofNMP were added 431 g of NaHCO3 (3.0 eq.) and 160 mE of methyl iodide (1.5 eq.) and the mixture was stirred at room temperature for 4 h. Afier cooling to 5° C. 1.71 E of 2N HC1 and 1.15 E of 20percent NaClaq were added to the mixture at less than 10° C. to give crystal of compound 7. Filtration, washing with 1.73 E of H20 and drying provided 507 g of compound P-7 (89percent yield) as a solid. ‘H NMR (300 MHz, DMSO-d5) ö 7.59 (d, J=7.5 Hz, 1H), 7.40-7.28 (m, 5H), 6.28 (d, J=7.5 Hz, 1H), 5.21 (d, J=5.4 Hz, 1H), 5.12 (d, J=10.8 Hz, 1H), 5.07 (d, J=10.8 Hz, 1H), 4.83 (t, J=5.7 Hz, 1H), 3.97 (dd, J=2.4, 14.1 Hz, 1H), 3.79 (s, 3H), 3.70 (dd, J=9.0, 14.4 Hz, 1H), 3.65-3.50 (m, 1H), 3.40-3.28 (m, 1H), 3.26-3.14 (m, 1H).To a slurry of 576 g of compound 6(1.0 eq.: 5.8percent of HStep E - Synthesis of Intermediate Compound A Into a 2-L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen. This was followed by the addition of 3-(benzyloxy)-l-(2, 3- dihydroxypropyl)-4-oxo-l, 4-dihydropyridine-2-carboxylic acid If (200 g, 626.35 mmol, 1.00 equiv), NMP (1000 mL), sodium bicarbonate (158 g, 1.88 mol, 3.00 equiv), CH

Molecular Weight:333.3
XLogP3:0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:8
Exact Mass:333.12123733
Monoisotopic Mass:333.12123733
Topological Polar Surface Area:96.3
Heavy Atom Count:24
Complexity:521
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes