Cesium carbonate → HCID 71279969, compound

Participants

Reaction Conditions

Reaction Steps

In a 2-(5 mL Biotage microwave vial were mixed N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (109 mg, 205 μmol), 3-chloro-N,N-dimethylpropan-1-aminium chloride (97.4 mg, 616 μmol, Eq: 3.0) and Cs2CO3 (402 mg, 1.23 mmol, Eq: 6.00) in DMF (2 mL). The mixture was stirred ˜10 min at 25° C. then heated to 100° C. in the Biotage microwave reactor for 30 min, diluted with 10 mL of dichloromethane and filtered through a celite pad, filtrate concentrated under high vacuum at 65° C. and residue dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (97 mg, 158 μmol, 76.7%) as a light brown solid. MS (M+H)+=616 (>90% purity); 1H NMR (CDCl3) δ: 9.24 (s, 1H), 8.36 (s, 1H), 8.32 (d, J=2.3 Hz, 1H), 8.06 (s, 1H), 7.60 (d, J=8.7 Hz, 1H), 7.35 (dd, J=9.1, 2.3 Hz, 1H), 6.55 (t, J=74.8 Hz, 1H), 5.75 (s, 2H), 4.60 (t, J=6.6 Hz, 2H), 3.53-3.74 (m, 2H), 2.33-2.42 (m, 2H), 2.29 (s, 6H), 2.14-2.27 (m, 2H), 1.65 (s, 9H), 0.90-1.07 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence