Lithium Hexamethyldisilazide → HCID 66611204, compound

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Reaction Steps

A solution of 2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (80.2 mg, 369 μmol) and 4-(2-fluoropyridin-3-yl)-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (112.0 mg, 357 μmol) in THF (1.0 mL) was stirred in an ice bath and treated dropwise with LHMDS (1.0 M in THF, 1.1 mL, 3 equiv.). The mixture was stirred for 45 min and then quenched with water (0.1 mL). The mixture was extracted into EtOAc from saturated aqueous NaHCO3, dried (MgSO4) and concentrated to give a dark residue. The residue was purified by flash chromatography on silica (25-30% EtOAc/hexane) to give N-(3-(6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pyridin-2-yl)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-amine (56.9 mg, 31.2% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 11.97 (br. s, 1H); 8.43-8.53 (m, 1H); 8.30-8.42 (m, 3H); 7.96 (br. s., 1H); 7.38-7.48 (m, 1H); 7.34 (d, J=7.43 Hz, 1H); 6.94-7.03 (m, 1H); 6.16 (d, J=10.17 Hz, 1H); 5.71 (d, J=9.00 Hz, 1H); 4.14 (d, J=9.98 Hz, 2H); 3.73-3.95 (m, 2H); 3.04 (s, 3H); 2.58-2.76 (m, 1H); 2.26-2.39 (m, 1H); 1.94-2.25 (m, 4H); 1.59-1.93 (m, 6H). m/z (ESI, +ve) 511.1 (M+H)+.

Provenance & Evidence