2-Amino-2-methyl-1-propanol → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

In a 16×100 mm screw cap test tube were added HATU (28.0 mg, 73.5 μmol.20) and 2-amino-2-methylpropan-1-ol (21.8 mg, 245 μmol) then 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (30 mg, 61.3 μmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution. The reaction mixture stirred at 25° C. overnight. TLC and LCMS showed incomplete reaction added 2-amino-2-methylpropan-1-ol (21.8 mg, 245 μmol) and HATU (28.0 mg, 73.5 μmol) and the reaction continued at 25° C. for 3 h. Solvents evaporated and residue purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 50% EtOAc in hexanes over 30 min to yield 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (34.4 mg, 61.3 μmol, 100%) as an off-white solid. 1H NMR (CDCl3) δ: 9.22 (s, 1H), 8.35 (s, 1H), 8.31 (s, 1H), 8.24 (d, J=2.3 Hz, 1H), 7.43-7.52 (m, 1H), 7.34 (dd, J=8.9, 2.1 Hz, 1H), 6.53 (t, J=75.0 Hz, 1H), 5.72 (s, 2H), 4.21 (s, 3H), 3.79 (s, 2H), 3.53-3.64 (m, 2H), 1.55 (s, 6H), 0.85-1.07 (m, 2H), −0.03 (s, 9H).

Provenance & Evidence