Sulfuric Acid → 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)piperidin-1-yl)-2-methylpropanamide

Participants

Reaction Steps

To 2-{4-[2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1.3a-diaza-benzo[e]azulen-8-yl]-piperidin-1-yl}-2-methyl-propionitrile (140 mg, 0.31 mmol) was added concentrated sulfuric acid (1.75 mL). The mixture was stirred at RT for 3.5 hours before the reaction was diluted with ice and neutralised with sodium carbonate. The aqueous mixture was extracted with 10% MeOH in DCM (×5) before the organic phase was dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash column chromatography (SiO2, gradient 0-10% MeOH in DCM). The material was triturated with diethyl ether before being purified by reverse phase HPLC (C18, gradient 20-70% MeOH/0.1% formic acid in water/0.1% formic acid). The resultant residue was taken up into MeOH (1.2 mL) and treated with 0.2 M HCl in diethyl ether. The solution was concentrated in vacuo affording 289 (14 mg, 0.03 mmol, 9%). LCMS: RT=2.65 min, [M+H]+=478. 1H NMR δ (ppm)(DMSO-d6): 9.50 (1 H, m), 8.33 (1 H, d, J=8.29 Hz), 7.97 (1 H, s), 7.93 (1 H, s), 7.86 (1 H, s), 7.02 (1 H, dd, J=8.36, 1.75 Hz), 6.87 (1 H, d, J=1.71 Hz), 5.78-5.71 (1 H, m), 4.50-4.44 (4 H, m), 3.19-3.04 (2 H, m), 2.91-2.80 (1 H, m), 2.25 (3 H, s), 2.12 (2 H, d, J=13.49 Hz), 1.98 (2 H, d, J=13.54 Hz), 1.51 (6 H, s), 1.43 (6 H, d, J=6.59 Hz). 2H obscured by solvent.

Provenance & Evidence