Hydrazine → HCID 58382062, compound

Participants

Reaction Conditions

Reaction Steps

The 2-(2-(3-(4-(2-hydroxypropan-2-yl)phenyl)-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)benzyl)isoindoline-1,3-dione (0.154 g, 0.226 mmol) in EtOH (4 mL) was treated with hydrazine (0.147 mL, 4.68 mmol) then heated to about 85° C. for about 15 min. The mixture was diluted with EtOAc (20 mL). The insoluble material was removed by filtration and washed with EtOAc (5 mL). The filtrate was concentrated under reduced pressure then the material was dissolved in 1,4-dioxane (4 mL) and treated with aqueous NaOH (50 wt %, 0.260 g, 3.25 mmol). The mixture was heated in a microwave at about 120° C. for about 20 min. The mixture was concentrated under reduced pressure then dissolved in AcOH (1 mL) and DMF (3 mL). The material was purified by preparative reverse phase HPLC (Table 2, Method i). The fractions with desired material were collected and lyophilized. The material was purified using a 5 g Si-Carbonate column (Silicycle™) and eluting wiht MeOH. The material was treated with EtOAc (˜10 mL) then concentrated under reduced pressure. This was repeated several times until a yellow solid was obtained. The material was triturated with EtOAc (3 mL) and heptane (15 mL) and the solid was collected by filtration and dried to constant weight under vacuum at about 70° C. to give 2-(4-(1-(2-(aminomethyl)phenyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-3-yl)phenyl)propan-2-ol (0.022 g, 25%): LC/MS (Table 2, Method a) Rt=1.62 min; MS m/z 398 (M+H)+. Syk IC50=B.

Provenance & Evidence