Triphenylphosphine → HCID 69897632, compound

Participants

Reaction Steps

Under nitrogen atmosphere, triphenylphosphine bound resin (1.22 g, 1.36 mmol, 1.12 mmol/g) was swelled in dichloromethane for 30 minutes. 3-(5-Methyl-3-phenylisoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-a]isoindol-8-ol (0.3 g, 0.91 mmol) (prepared as in Example 3, Step (a)), 4-hydroxy-boc-piperidine (0.27 g, 1.36 mmol, 1.5 eq.) and diethyl azodicarboxylate (0.21 ml, 1.36 mmol, 1.5 eq.) were added and the reaction was stirred at room temperature overnight. The resin was filtered off and washed with dichloromethane, methanol and ether. The combined organics were concentrated in vacuo. The residue was purified by alumina chromatography, eluting with dichloromethane 2% methanol/dichloromethane (0.5% methanol gradient), and was used without further purification in the next step. b) 3-(5-Methyl-3-phenylisoxazol-4-yl)-8-(piperidin-4-yloxy)-5H-[1,2,4]triazolo[3,4-α]isoindole 4-[3-(5-Methyl-3-phenylisoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindol-8-yloxy]-piperidine-1-carboxylic acid tert-butyl ester (466 mg, 0.91 mmol) was dissolved in TFA (5 ml) and stirred at room temperature for 1 hour. The reaction was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated K2CO3 (aq). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by alumina chromatography, eluting with dichloromethane→5% methanol/dichloromethane (in 1% methanol gradient), to afford the title compound as a white solid (4 mg, 1% over 2 steps). 1H NMR (400 MHz, d4 MeOH) δ 7.53–7.43 (6H, m), 7.32 (1H, d, J=8.5 Hz), 7.08 (1H, dd, J=8.5, 2.4 Hz), 4.63–4.60 (1H, m), 4.24 (2H, s), 3.16–3.11 (2H, m), 2.85–2.79 (2H, m), 2.64 (3H, s), 2.09–2.05 (2H, m), 1.78–1.72 (2H, m). m/z (ES+) 414 (M+H)+.

Provenance & Evidence