Dimethylcarbamoyl Chloride → Hydrochloric Acid

Participants

Reaction Steps

(R)-5-(3-(3,3-Dimethylureido)piperidin-1-yl)-3-(4-(4-methylpiperidin-4-yl)phenylamino)pyrazine-2-carboxamide (289) (90 mg, 0.2 mmol) was dissolved in 4 mL NMP. To it were added DIEA (350 μL, 2.0 mmol) and then dimethylcarbamoyl chloride (55 μL, 0.6 mmol). The mixture was stirred at RT for 30 min, quenched with 0.5 mL TFA, and directly subjected to reverse phase prep HPLC using 5 mM HCl (aq) and neat MeCN as mobile phases to isolate (R)-3-(4-(1-(dimethylcarbamoyl)-4-methylpiperidin-4-yl)phenylamino)-5-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (291) as HCl salt (61 mg, 55%). MS found for C28H41N9O3 as (M+H)+ 552.4, (M−H)− 550.3. UV: λ=268, 277, 305, 336, 372 nm Proton NMR (CD3OD): δ 7.63 (1H, s), 7.61 (2H, d, J=8.5 Hz), 7.32 (2H, d, J=8.5 Hz), 4.37 (1H, m), 4.21 (1H, m), 3.77 (1H, m), 3.37-3.31 (2H, m), 3.21-3.15 (3H, m), 3.10 (1H, m), 2.88 (6H, s), 2.83 (6H, s), 2.15 (2H, m), 2.02 (1H, m), 1.87 (1H, m), 1.75-1.63 (4H, m), 1.26 (3H, s) ppm.

Provenance & Evidence