Acetic Acid → HCID 135974936, compound

Participants

Reaction Steps

To a solution of 2-[4-(4-amino-phenylethynyl)-1-methyl-1H-pyrazol-3-yl]-4-methyl-phenol (1) (15.2 g, 50 mmol) and N-Boc-2-piperidinecarboxylic acid (2) (34.4 g, 150 mmol) and 4-dimethylaminopyridine (DMAP, 0.6 g, 5 mmol) in dry dichloromethane (600 mL) was added N,N′-diisopropylcarbodiimide (DIPC, 23.3 mL, 150 mmol) slowly. The reaction mixture was stirred at rt overnight. Water (˜100 mL) was added, and the mixture was stirred at rt for one hour. The organic layer was collected, filtered and concentrated. To the resultant residua was added THF (200 mL) and methanol (200 mL). A solution of lithium hydroxide monohydrate (21 g, 500 mmol) in water (100 mL) was slowly added above solution. The mixture was stirred at rt for 2 hours. It was then neutralized with acetic acid (29 mL, 500 mmol). The mixture was diluted with ethyl acetate (˜300 mL), and washed with brine, and dried over sodium sulfate. It was filtered, concentrated and purified with silica column chromatography eluting with dichloromethane-ethyl acetate (v/v 9/1). After crystallizing with hexanes/ethyl acetate, the title compound (3, 20.09 g) was obtained as white powder in 78% yield. 1H NMR (CDCl3, 500 MHz) δ 10.48 (s, 1H), 8.41 (s, 1H), 7.60 (s, 1H), 7.54 (d, 2H, J=8.0 Hz), 7.48 (d, 2H, J=8.0 Hz), 7.06 (d, 1H, J=8.0 Hz), 6.94 (d, 1H, J=8.0 Hz), 4.88 (br s, 1H), 4.08 (br s, 1H), 3.94 (s, 3H), 2.87 (t, 1H, J=6.1 Hz), 2.34 (s, 3H), 1.76-1.55 (m, 4H), 1.53 (s, 9H), 1.47 (m, 1H), 1.27 (m, 1H). LCMS (ESI) m/z 515.16 (MH+, 100), 415.15; HPLC: tR=6.88 min.

Provenance & Evidence