Acetic Acid → 5-(5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-(4-chlorophenyl)-1-(2-methoxypyridin-3-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5-(3-acetyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)-3-chloro-1-methylpyridin-2(1H)-one (Step 57.1) (250 mg, 0.636 mmol) and TEA (0.115 ml, 0.827 mmol) in EtOH (2 ml) was added 3-hydrazinyl-2-methoxypyridine (Step 71.1) (115 mg, 0.827 mmol) and the reaction mixture was stirred 1 hr at 90° C. Sulfamic acid (93 mg, 0.954 mmol) and AcOH (2 ml) was added and the reaction mixture was stirred 3 hr at 115° C. The reaction mixture was concentrated under reduced pressure, quenched with a saturated aq. NaHCO3 solution and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with EtOAC. The residue was further purified by SFC (column Propyl-pyridyl-urea, gradient 13-18% in 6 min_total 11 min) and triturated in hexane/Et2O (2:1) to afford the title product (13 mg, 0.026 mmol, 4% yield) as white solid. tR: 4.55 min (HPLC 1); tR: 1.04 min (LC-MS 2); ESI-MS: 496 [M+H]+ (LC-MS 2); Rf=0.41 (EtOAc); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.02 (s, 3H) 3.43 (s, 3H) 3.89 (s, 3H) 6.24 (s, 1H) 7.15-7.22 (m, 1H) 7.32-7.37 (m, 2H) 7.40-7.45 (m, 2H) 7.88-7.96 (m, 3H) 8.28-8.33 (m, 1H).

Provenance & Evidence