Ethylenediamine → HCID 58382033, compound

Participants

Reaction Conditions

Reaction Steps

To a round bottom flask was added (9H-fluoren-9-yl)methyl (7-(5-methoxy-1-methyl-1H-indol-3-yl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)methylcarbamate (0.300 g, 0.429 mmol, prepared using J.1 from Preparation #I.1 with 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)acetic acid and L.1 with mercury(II) trifluoroacetate), DMF (10 mL), TBAF (1.0 M in THF, 1.72 mL, 1.72 mmol) and ethylenediamine (0.870 mL, 12.9 mmol). The mixture was heated to about 85° C. for about 6 h. The mixture was cooled to rt and concentrated in vacuo. The crude material was purified by flash chromatography (120 g silica gel column, DCM/MeOH 1:0 to 10:1). The solid was purified by reverse phase preparatory HPLC (Table 2, Method e) to give fractions with the title compound. The fractions were combined and concentrated in vacuo until a precipitate formed. The solid was collected by vacuum filtration and then dried under reduced pressure at about 60° C. for about 16 h to give (7-(5-methoxy-1-methyl-1H-indol-3-yl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)methanamine (0.021 g, 14%): LC/MS (Table 2, Method a) Rt=1.53 min; MS m/z 347 (M+H)+. Syk IC50=B.

Provenance & Evidence