Trifluoroacetic acid → 4-Bromo-1-(2,2-dimethylpropyl)-5-(pyrazin-2-ylmethoxy)-1H-1,2,3-benzotriazole

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Reaction Steps

To a suspension of 4-bromo-1-(2,2-dimethylpropyl)-1H-1,2,3-benzotriazol-5-ol (Example 1-2) (1.5 g, 5.28 mmol, 1.0 equiv.), 2-pyrazinylmethanol (13) (0.581 g, 5.28 mmol, 1.0 equiv.) and polymer-supported triphenylphosphine (2.2 mmol/g, 5.75 g, 21.91 mmol, 2.5 equiv.) in THF (37.7 ml) and DCM (37.7 ml) was slowly added di-tert-butyl azodicarboxylate (2.431 g, 10.56 mmol, 2.0 equiv.). After stirring at room temperature for 1 hr, the reaction mixture was passed through a filter. The residue was washed with DCM and THF. The filtrate was concentrated to dryness to give a solid, which was taken up in DCM (12 mL) and treated with TFA (6 mL). The mixture was stirred at room temperature until LCMS showed only the desired product. The reaction mixture was neutralized to pH=7 with saturated aqueous NaHCO3, and then extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (EtOAc/Hexane gradient from 0 to 100%) to obtain product Example 4-1. 1H NMR δ (CDCl3): 9.06 (s, 1H), 8.59-8.57 (m, 2H), 7.42 (d, 1H, J=9.5 Hz), 7.31 (d, 1H, J=9.0 Hz), 5.38 (s, 2H), 4.38 (s, 2H), 1.04 (s, 9H) ppm. LRMS m/z (M+H) 376.1 and 378.1 (intensity ratio ˜1:1) found, 376.1 and 378.1 required.

Provenance & Evidence