1,2-Dichloroethane → 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) (190 mg, 0.4 mmol) was dissolved in 20 mL DCE and 20 mL dioxane. To it were added DIEA (350 μL, 2.0 mmol) and cyclopentanone (710 μL, 8.0 mmol). The mixture was stirred at RT for 2 hours, and to it were added HOAc (250 μL, 4.0 mmol) and NaBH(OAc)3 (430 mg, 2.0 mmol). The mixture was stirred at RT for 1.5 hour. It was diluted with 10 mL MeOH, concentrated in vacuo, acidified 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-cyclopentyl-4-methylpiperidin-4-yl)phenylamino)-5-(3-(3,3-dimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (290) as HCl salt (82 mg, 37%). MS found for C30H44N8O2 as (M+H)+ 549.6. UV: λ=268, 278, 306, 336, 373 nm. Proton NMR (CD3OD): δ 7.71-7.63 (3H, m), 7.36-7.33 (2H, m), 4.38-4.32 (1H, m), 4.22 (1H, m), 3.77 (1H, m), 3.66-3.50 (2H, m), 3.28-3.10 (2H, m), 2.89 (6H, s), 2.86-2.80 (2H, m), 2.64 (1H, m), 2.23-1.62 (16H, m), 1.42-1.26 (3H, s) ppm.

Provenance & Evidence