Aluminium lithium hydride → 2-(4-{3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]-pyridin-5-yl}-pyrazol-1-yl)-2-methylpropan-1-ol

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Reaction Conditions

Reaction Steps

To a solution of 2-(4-{3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]-pyridin-5-yl}-pyrazol-1-yl)-2-methylpropionic acid methyl ester (64.0 mg, 0.135 mmol) in THF (3.0 mL) was added 2 M of LiAlH4 in THF (0.20 mL, 0.40 mmol) under N2 at −78° C. The reaction mixture was stirred for 1 h at −78° C., quenched by adding water, warmed to rt, filtered, and concentrated in vacuo. Purification of the residue by HPLC afforded the title compound. A crystal structure of the title compound bound to cMet confirmed the absolute configuration as shown. 1H NMR (400 MHz, CD3OD): δ=1.58 (s, 6 H), 1.88 (d, J=7.2 Hz, 3 H), 3.75 (s, 2 H), 5.28 (q, J=7.2 Hz, 1H), 7.18 (t, J=8.6 Hz, 1 H), 7.35 (d, J=1.3 Hz, 1 H), 7.37-7.39 (m, 1H), 7.41 (brs, 1H), 7.58 (s, 1 H), 7.91 (s, 1 H), 8.32 (d, J=1.8 Hz, 1H). MS (ES+): m/z 447.09/449.04 (100/70) [MH+]. HPLC: tR=3.50 min (ZQ3 polar—5 min).

Provenance & Evidence