Picolyl chloride hydrochloride → HCID 67102291, compound

Participants

Reaction Steps

To a DMF (1 mL) solution of 1-[2-(1H-Indol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (50 mg, 0.11 mmol; prepared as described in Ex. 45, only using the Sem-protected starting material) was added NaHMDS (0.25 mL, 1M in THF) and stirred for 20 min at RT. 2-Chloromethylpyridine hydrochloride (21.6 mg, 0.13 mmol) was added in a single portion. After stirring for 1 hr at RT TLC analysis (25% EtOAc/hexanes) shows a new more-polar product. The reaction mixture was poured into 25 mL of saturated sodium bicarbonate solution and extracted with EtOAc (2×15 mL). The organic layers were combined, washed with brine, dried over MgSO4, and concentrated to give a yellow oil. Chromatography (SiO2; 0%-13%-25% EtOAc in hexanes) gives 2,2-Dimethyl-1-[2-(1-pyridin-2-ylmethyl-1H-indol-5-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one as a clear oil. Following general procedures as described in these Examples, the SEM group was removed to give 2,2-Dimethyl-1-[2-(1-pyridin-2-ylmethyl-1H-indol-5-yl)-5Hpyrrolo[2,3-b]pyrazin-7-yl]propan-1-one (47%; MS=410 [M+H]; MP: 194-196° C.).

Provenance & Evidence