Cesium carbonate → HCID 71279997, 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 (60 mg, 113 μmol), 4-(3-chloropropyl)morpholine (55.5 mg, 339 μmol, Eq: 3.0) and Cs2CO3 (147 mg, 452 μmol) 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. Then, 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-morpholinopropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (62 mg, 94.2 μmol, 83.4%) as an off-white solid. MS (M+Na)+=680; 1H NMR (CDCl3) δ: 9.23 (s, 1H), 8.36 (s, 1H), 8.32 (d, J=2.3 Hz, 1H), 8.05 (s, 1H), 7.59 (d, J=9.1 Hz, 1H), 7.35 (dd, J=8.9, 2.1 Hz, 1H), 6.55 (t, J=74.4 Hz, 1H), 5.75 (s, 2H), 4.61 (t, J=6.4 Hz, 2H), 3.75 (br. s., 4H), 3.55-3.66 (m, 2H), 2.45 (br. s., 6H), 2.25 (br. s., 2H), 1.65 (s, 9H), 0.90-1.06 (m, 2H), 0.00 (s, 9H).

Provenance & Evidence