Aluminium lithium hydride → 1-(4-(2-(5-(3-Hydroxypropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone

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Reaction Steps

A solution of methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (100 mg, 0.195 mmol) in THF (10 mL) at 0° C. was treated dropwise with LiAlH4 (1M in THF, 195 μL, 0.195 mmol). Once the addition was completed the ice bath was removed and the mixture was stirred at ambient temperature for 30 minutes. The mixture was cooled to 0° C. and quenched with successive addition of water (0.2 mL), 2N NaOH (0.6 mL), and water (0.2 mL). The mixture was stirred at ambient temperature for 30 minutes and the resulting solids were removed by filtration, washing with additional THF. The filtrate was concentrated in vacuo and the residue was purified by reverse phase C-18 chromatography using a gradient of 20%-90% CH3CN/water to provide the title compound (20 mg, 0.0413 mmol, 21.2% yield) as a white solid. 1H NMR (DMSO-d6) δ 10.77 (brs, 1H), 8.11 (s, 1H), 7.42 (m, 2H), 7.86 (s, 1H), 7.18 (m, 1H), 7.06 (d, 2H), 6.66 (s, 1H), 4.49 (t, 1H), 4.42 (d, 1H), 3.85 (d, 1H), 3.44 (q, 2H), 3.12 (t, 1H), 2.88 (t, 2H), 2.80 (m, 1H), 2.62 (t, 1H), 2.00 (s, 3H), 1.92 (t, 2H), 1.66-1.59 (m, 2H), 1.57-1.41 (m, 2H).

Provenance & Evidence