Ethanol → HCID 66993632, compound

Participants

Reaction Steps

To a solution of Intermediate No. 2 (0.70 g, 2.92 mmol) in 30 mL of dichloroethane (DCE), was added MnO2 (2.67 g, 17.5 mmol). After being stirred for 4 hours at 70° C., the reaction mixture was passed through a pad of Celite and rinsed with dichloromethane. The filtrate was concentrated in vacuo to give a desired Intermediate No. 4 as a pale yellow solid (0.6 g, 87%). A solution of Intermediate No. 4 (311 mg, 1.32 mmol) and 2-(piperazin-1-yl)ethanol (0.23 g, 1.77 mmol) in 10 mL of dichloromethane (DCM) was stirred for 20 minutes at room temperature. To this, was added NaBH(OAc)3 (0.58 g, 2.6 mmol) at room temperature. The reaction was stirred for 3 hours at room temperature and then quenched with 1N-NaOH. It was extracted with ethyl acetate and washed twice with brine. The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacou. The resulting residue was purified by silica gel chromatography to afford desired intermediate No. 5 as a white solid (0.42 mg, 91%). A 2 dram vial was charged with 2-(4-(1-(2-chloro-5-methylpyrimidin-4-yl)-4-methyl-1H-pyrrol-3-yl)methyl)piperazin-1-yl)ethanol (Intermediate No. 5) (70 mg, 0.2 mmol), 3,4,5-trimethoxyaniline (48 mg, 0.26 mmol), 83 mg (0 6 mmol) of potassium carbonate, Pd(dppf)Cl2 (8 mg), BYNAP (12 mg) and 3 mL of anhydrous dioxane. After being degassed by nitrogen bubbling, the reaction mixture was heated at 100° C. for 16 hours and cooled to room temperature. The resulting insolubles were removed by filtration and then the filtrate was concentrated in vacuo. The resulting dark brown residue was purified by silica gel chromatography (5 to 15% MeOH/DCM) to afford desired Compound 40 as a pale yellow solid (74 mg, 75%); 1H NMR (300 MHz, CDCl3) δ 9.43 (s, 1H), 8.34 (s, 1H), 7.39 (s, 1H), 7.30 (s, 1H), 7.18 (s, 2H), 3.77 (s, 9H), 3.61 (s, 2H), 3.45 (m, 2H), 3.21 (m, 2H), 2.38-2.32 (m, 8H), 2.19 (s, 3H), 2.03 (s, 3H); MS (ESI) m/z 497 [M+1-1]+.

Provenance & Evidence