Hydrochloric Acid → 2-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenylamino)-4-(4-fluorophenyl)-4,5-dihydrobenzo[d]thiazol-6(7H)-one

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Reaction Steps

A mixture of N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-4-(4-fluorophenyl)-5,7-dihydro-4H-spiro[benzo[d]thiazole-6,2′-[1,3]dioxolan]-2-amine (54 mg, 0.105 mmol, example 74), aqueous 1.0 M HCl (0.16 mL), and acetone (0.13 mL) was heated at reflux for 24 h. Partial conversion of the starting material to the desired product was evident by LCMS analysis of a crude aliquot. An additional portion of aqueous 1.0 M HCl (0.20 mL) was added and the acetone was removed in vacuo. The resulting mixture was heated at 75° C. for an additional 24 h. The crude reaction was quenced with saturated sodium bicarbonate solution and extracted with EtOAc. The organic layer was concentrated in vacuo. The crude product was purified using preparatory TLC (50% acetone/hexanes) to give 22 mg (43% yield) of the titled compound as an oil. LC-MS (M+H)+ 469.2. 1H NMR (400 MHz, chloroform-d) δ ppm 7.54 (d, J=1.51 Hz, 1 H) 7.46 (d, J=2.52 Hz, 1 H) 7.09-7.20 (m, 3 H) 6.94-7.07 (m, 3 H) 6.77 (dd, J=8.44, 2.39 Hz, 1 H) 4.46 (t, J=6.42 Hz, 1 H) 3.63-3.67 (m, 2 H) 3.62 (s, 3 H) 3.08 (dd, J=14.35, 6.55 Hz, 1 H) 2.86 (dd, J=14.23, 6.42 Hz, 1 H).

Provenance & Evidence