反应详情

The product of Example 65, 1-methyl-6-oxo-4-(2,3,4-trichloro-phenylamino)-1,6-dihydro-pyridine-3-carboxylic acid (0.4 g, 1.15 mmol) was dissolved in DCM (20 mL). Added one drop of DMF and then oxalyl chloride (0.11 mL, 1.27 mmol) was added. Reaction was stirred at rt for 1.5 hours. Then 0.5 N NH3/dioxane (10 mL) was added and stirred for 72 hours. The solvent was removed in vacuum. Ethyl acetate was added and washed with sat. NaHCO3 soln. Filtered solid and dried in vacuum oven 1 hour. Tried to recrystalize using hexanes (5 mL) and EtOAc (30 mL) but never dissolved. Solvent removed in vacuum and took the residue up in ethyl acetate (10 mL)/MeOH (2 mL). Still did not dissolve. Cooled, filtered and dried in vacuum oven overnight at 60° C. Obtained white solid (210.0 mg, 52.7% y.). MS (APCI+) 347,349 [M+H]; HPLC 2.954 m. 94.68%; C13H10Cl3N3O2; CHN Calc. C)45.05% H)2.91% N)12.12% found C)27.56% H)1.29% N)3.96%; NMR (400 MHz, DMSO-d6) δ 13.36 (s, 1H), 8.11 (s, 1H), 7.55 (d, J=9.0 Hz, 1H), 7.51 (d, J=9.0 Hz, 1H), 5.67 (s, 1H), 3.31 (s, 3H).

1. customReaction
2. stirringstirred for 72 hours
3. customThe solvent was removed in vacuum
4. additionEthyl acetate was added
5. washwashed with sat. NaHCO3 soln
6. filtrationFiltered solid
7. customdried in vacuum oven 1 hour
8. customTried to recrystalize
9. dissolutionnever dissolved
10. customSolvent removed in vacuum
11. dissolutionStill did not dissolve
12. temperatureCooled
13. filtrationfiltered
14. customdried in vacuum oven overnight at 60° C
15. customObtained white solid (210.0 mg, 52.7% y.)