Diisopropylethylamine → 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide

Participants

Reaction Steps

In a 100 mL round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1.0 g, 2.69 mmol) was combined with dichloromethane (3 ml) to give a yellow solution. (R)-1-Benzylpyrrolidin-3-amine (710 mg, 4.03 mmol) and then DIEA (1.88 ml, 10.7 mmol) were added. To the clear solution was added HATU (2.04 g, 5.37 mmol) and to this mixture was added DMF (4 ml). The reaction was stirred under nitrogen overnight then concentrated and partioned between water (100 ml) and EtOAc (100 ml). The aqueous layer was washed with EtOAc (50 ml) then the combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude was dissolved in EtOAc, supported on silica gel, and purified by flash chromatography (120 g silicycle) with 0% to 100% EtOAc in hexanes. The appropriate fractions combined and concentrated to yield 1.38 g (97%) of 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-benzyl-pyrrolidin-3-yl)-amide as a clear viscous semisolid with a slight red/brown tint. LC-MS (M+H)+=530.

Provenance & Evidence