3-bromocyclohexane-1,2-dione

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3-bromocyclohexane-1,2dione (158 mg, 0.827 mmol, from preparation AAE) and 1-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)thiourea (109 mg, 0.414 mmol, from step 4 of preparation F) was heated in ethanol (1.4 mL) at 80° C. for 12 h. The crude reaction was diluted with EtOAc and washed with saturated sodium bicarbonate solution. The organic layer was concentrated in vacuo. The crude product was purified using preparatory TLC (80% acetone/hexanes) to afford 2-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenylamino)-6,7-dihydrobenzo[d]thiazol-4(5H)-one (64 mg, 44% yield) as a yellow solid. LC-MS (M+H)+ 356.3. 1H NMR (400 MHz, chloroform-d) δ ppm 8.55 (s, 1 H) 7.68 (d, J=8.56 Hz, 1 H) 7.31 (d, J=2.27 Hz, 1 H) 6.96 (dd, J=8.56, 2.52 Hz, 1 H) 3.95 (s, 3H) 3.00 (t, J=6.04 Hz, 2 H) 2.59-2.68 (m, 2 H) 2.45-2.52 (m, 3H) 2.20-2.31 (m, 2H). The crude reaction washed with saturated sodium bicarbonate solution The organic layer was concentrated in vacuo The crude product was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Step AAE (1): Followed the method of B. Miller and H.-S. Wong Tetrahedron 1972, 28, 2369. Bromine (0.651 mL, 12.6 mmol) in was added dropwise to a solution of cyclohexane-1,2-dione (1.35 g, 12.0 mmol) in CCl4 (30 mL) at 0° C. The reaction mixture was allowed to warm to rt. The resulting solution was concentrated in vacuo to afford 3-bromocyclohexane-1,2-dione. The crude product, which is prone to decomposition, was used for subsequent chemistry without purification or characterization. The resulting solution was concentrated in vacuo

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of toluene/t-butanol (1:1) is added 2-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-piperazin-1-yl]-thioacetamide (180 mg, 0.45 mmol) and 3-bromo-cyclohexane-1,2-dione (135 mg, 0.80 mmol). The reaction is heated at 90° C. for 4 h and is then concentrated and crude product is dissolved in CH2Cl2 and washed with NaHCO3. The solution is concentrated and purified using 1% MeOH/EtOAc to provide 2-[4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-ylmethyl]-6,7-dihydro-5H-benzothiazol-4-one. 1H NMR (300 MHz, CDCl3) δ7.87-7.82 (m, 3H), 7.47 (dd, 1H), 4.80 (s, 2H), 3.91 (s, 2H), 3.61 (t, 2H), 3.43 (t, 2H), 3.05 (t, 2H), 2.65 (t, 2H), 2.24 (dt, 2H); MS (Ion Spray) 496 (M+H)+. is then concentrated crude product is dissolved in CH2Cl2 washed with NaHCO3 The solution is concentrated purified