Lithium Hexamethyldisilazide → N-(5-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine

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Reaction Steps

A solution of 6-(5-chloro-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (75.3 mg, 217 μmol) and 1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (49.4 mg, 227 μmol) in THF (1.0 mL) was cooled in an ice bath and treated dropwise with LiHMDS in THF (0.68 mL of 1.0 M solution, 3 equiv.) giving a deep red solution. The mixture was stirred for 45 min and then quenched with water (0.1 mL). Extraction into EtOAc from saturated aqueous NaHCO3, drying (MgSO4) and concentration gave a deep yellow oil. Purification by flash chromatography on silica eluting with 40% EtOAc/hexane gave N-(5-chloro-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (96.8 mg, 82.0% yield) (yellow band on column) as a bright yellow solid. 1H NMR (400 MHz, CDCl3) δ 12.70 (br. s., 1H); 9.82 (d, J=2.74 Hz, 1H); 8.21-8.40 (m, 3H); 8.06 (dd, J=7.53, 1.66 Hz, 1H); 7.42 (t, J=8.02 Hz, 1H); 7.20-7.30 (m, 1H); 5.87 (dd, J=10.47, 2.25 Hz, 1H); 5.72 (dd, J=9.59, 2.54 Hz, 1H); 4.15-4.28 (m, 1H); 4.02-4.12 (m, 1H); 3.70-3.88 (m, 2H); 3.00 (s, 3H); 2.52-2.71 (m, 1H); 1.98-2.27 (m, 5H); 1.58-1.92 (m, 6H). m/z (ESI, +ve) 545.1 (M+H)+.

Provenance & Evidence