1,2-Dichloroethane → Hydrochloric Acid

Participants

Reaction Steps

Crude (R)-3-(4-(piperidin-4-yl)phenylamino)-5-(3-(1,3,3-trimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (297) (100 mg, 0.18 mmol) was dissolved in 10 mL DCE and 10 mL dioxane. To it were added DIEA (160 μL, 0.90 mmol) and cyclopentanone (320 μL, 3.60 mmol). The mixture was stirred at RT for 2 hours, and to it were added HOAc (100 μL, 1.8 mmol) and NaBH(OAc)3 (190 mg, 0.90 mmol). The mixture was stirred at RT for overnight. 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-cyclopentylpiperidin-4-yl)phenylamino)-5-(3-(1,3,3-trimethylureido)piperidin-1-yl)pyrazine-2-carboxamide (298) as HCl salt (29 mg, 29%). MS found for C30H44N8O2 as (M+H)+ 549.6. UV: λ=269, 276, 306, 335, 373 nm. Proton NMR (CD3OD): δ 7.64 (1H, s), 7.57 (2H, d, J=8.5 Hz), 7.21 (2H, d, J=8.5 Hz), 4.53 (1H, m), 4.35 (1H, m), 3.72 (1H, s), 3.70 (1H, s), 3.56 (2H, m), 3.20 (1H, m), 3.13 (2H, m), 3.00 (1H, m), 2.85 (1H, m), 2.83 (3H, s), 2.77 (6H, s), 2.21 (2H, m), 2.12 (2H, m), 2.03-1.65 (12H, m) ppm.

Provenance & Evidence