1-Hydroxybenzotriazole → 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide

Participants

Reaction Steps

A 25 mL round-bottomed flask was charged with 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.39 g, 0.84 mmol), (S)-1-methoxypropan-2-amine hydrochloride (253 mg, 2.0 mmol), HBTU (457 mg, 1.27 mmol), and HOBT (125 mg, 0.93 mmol). Then added DMF (2 mL) followed by N,N-diisopropylethylamine (0.59 mL, 3.38 mmol). The yellow reaction mixture was stirred at room temperature overnight then quenched with water and extracted with EtOAc (30 mL). The organic layer was washed once with saturated NaHCO3 and water. The combined aqueous layers were back extracted with EtOAc (25 mL). The combined organic layers was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over SiO2 with EtOAc/heptane (gradient: 0-100% EtOAc) to afford 401 mg (89%) of 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a light yellow solid. MS: [M+H]+=533.

Provenance & Evidence