2-Amino-2-methyl-1-propanol → N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-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 (40.2 mg, 106 μmol.20) and 2-amino-2-methylpropan-1-ol (31.4 mg, 353 μmol) then 2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (40 mg, 88.2 mmol) dissolved in DMF (2.00 mL) was added to give a light yellow solution. The reaction mixture stirred at 25° C. overnight, 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 25 min to yield N-(1-hydroxy-2-methylpropan-2-yl)-2-(5-methoxy-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (46.3 mg, 88.2 μmol, 100%) as an off-white solid. MS (M+Na)+=547 (>90% purity); 1H NMR (CDCl3) δ: 9.14 (s, 1H), 8.49 (s, 1H), 8.32 (s, 1H), 7.85 (d, J=2.3 Hz, 1H), 7.41 (d, J=9.1 Hz, 1H), 7.20 (dd, J=9.3, 2.5 Hz, 1H), 5.72 (s, 2H), 4.18 (s, 3H), 3.92 (s, 3H), 3.78 (s, 2H), 3.54-3.65 (m, 2H), 1.53 (s, 6H), 0.91-1.01 (m, 2H), −0.03 (s, 9H).

Provenance & Evidence