Pyridine → HCID 86292589, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 81.1) (200 mg, 0.542 mmol) in CAN (4 mL) with molecular sieves (4 g) under Ar were added 2-methylpyridine-3-boronic acid (166 mg, 1.085 mmol), pyridine (0.088 mL, 1.085 mmol) and copper(II) acetate (148 mg, 0.813 mmol) and the reaction mixture was stirred 10 min at 65° C. 2-methylpyridine-3-boronic acid (1.485 g, 10.85 mmol) was added portionwise over a period of 1 hr. The reaction mixture was concentrated under reduced pressure, quenched with a saturated aq. NaHCO3 solution and the aq. layer was extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 1.5-5%). followed by preparative achiral SFC (column 4-Ethyl-pyridine, gradient 13-18% in 6 min_total 11 min) and triturated in Hexane/Et2O (1:1) to afford the title product (11 mg, 0.024 mmol, 4% yield). tR: 3.20 min (HPLC 1); tR: 0.87 min (LC-MS 2); ESI-MS: 460 [M+H]+ (LC-MS 2); Rf=0.53 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6)6 ppm 1.89 (s, 3H) 1.93 (s, 3H) 2.18 (s, 3H) 3.37 (s, 3H) 6.23 (s, 1H) 7.28-7.49 (m, 6H) 7.77 (d, J=2.7 Hz, 1H) 7.88 (dd, J=7.8, 1.56 Hz, 1H) 8.63 (dd, J=4.9, 1.4 Hz, 1H).

Provenance & Evidence