10,11-二氢二苯并[B,F][1,4]噁杂-11-酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 10,11-dihydro-dibenz[b,f][1,4]oxazepin-11-one (0.4 g; 1.9 mmol; Aldrich) in dry toluene (20 mL) at room temperature was added 2,6-dimethyl piperazine (0.99 g; 8.7 mmol; Aldrich) followed by the dropwise addition of TiCl4 (1M in toluene, 2.27 mL; 2.27 mmol). The reaction mixture was refluxed for 2 hours, cooled to room temperature and then poured into an ammonium hydroxide solution (30%, 50 mL). The resulting mixture was extracted with dichloromethane (4×75 mL), and the combined organic phases were then dried (K2CO3) and concentrated. Purification of the product was conducted on silica gel using CHCl3 :MeOH (94:6) eluant to give 0.353 g (60%) of 11-(3,5-dimethyl-1-piperazinyl)-dibenz[b,f][1,4]oxazepine as a pale yellow solid; m.p. 112°-114° C. The reaction mixture was refluxed for 2 hours The resulting mixture was extracted with dichloromethane (4×75 mL) the combined organic phases were then dried (K2CO3) concentrated Purification of the product

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 10,11-dihydro-dibenz[b,f][1,4]oxazepin-11-one in dry toluene at room temperature was added piperazine (Aldrich) followed by the dropwise addition of TiCl4. The reaction mixture was refluxed for 2 hours, cooled to room temperature and then poured into an ammonium hydroxide solution. The resulting mixture was extracted with dichloromethane, and the combined organic phases were then dried (K2 CO3) and concentrated. Purification of the product was conducted on silica gel using ethyl acetate:hexane (5:1→4:1) as the eluant to give 11-(1-piperazinyl)dibenz[b,f][1,4]oxazepine. The reaction mixture was refluxed for 2 hours The resulting mixture was extracted with dichloromethane the combined organic phases were then dried (K2 CO3) concentrated Purification of the product

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The starting material 10,11-dihydro-dibenz[b,f][1,4]oxazepin-11-one was prepared according to the procedures reported in Coyne et al (J. Med. Chem., 1967, 10:541). Briefly, this entailed coupling potassium salicylaldehyde with 2-chloronitrobenzene, followed by oxidation to the carboxylic acid, reduction of nitro, and finally ring closure, to yield the desired starting material. to yield the

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 11-oxo-dibenz[b,f][1,4]oxazepine (Aldrich) (0.149 g, 0.0007 mol) in dry toluene (10 mL), was added (1S,4S)-2-benzyl-2,5-diazabicyclo(2.2.1)heptane (0.54 g, 0.003 mol) and TiCl4 (0.75 mL, 0.0008 mol) via syringe. The mixture was stirred at room temperature for 30 rain then refluxed for 5 hrs. The reaction mixture was cooled and dumped into conc. NH4OH and extracted with CHCl3. The combined organic phases were dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed (hexane:EtOAc, 1:1) to give 11-(2-benzyl-2,5-diazabicyclo(2.2.1) hept-5-yl)-dibenz[b,f][1,4]oxazepine (yield 0.131 g, mp 70°-72° C.). then refluxed for 5 hrs The reaction mixture was cooled extracted with CHCl3 The combined organic phases were dried (MgSO4) concentrated in vacuo The crude material was chromatographed (hexane:EtOAc, 1:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 11-oxo-dibenz[b,f][1,4]oxazepine (Aldrich) (0.149 g, 0.0007 mol) in dry toluene (10 mL), was added (1S,4S)-2-benzyl-2,5-diazabicyclo(2.2.1)heptane (0.54 g, 0.003 mol) and TiCl4 (0.75 mL, 0.0008 mol) via syringe. The mixture was stirred at room temperature for 30 rain then refluxed for 5 hrs. The reaction mixture was cooled and dumped into conc. NH4OH and extracted with CHCl3. The combined organic phases were dried (MgSO4) and concentrated in vacuo. The crude material was chromatographed (hexane:EtOAc, 1:1) to give 11-(2-benzyl-2,5-diazabicyclo(2.2.1) hept-5-yl)-dibenz[b,f][1,4]oxazepine (yield 0.131 g, mp 70°-72° C.). then refluxed for 5 hrs The reaction mixture was cooled extracted with CHCl3 The combined organic phases were dried (MgSO4) concentrated in vacuo The crude material was chromatographed (hexane:EtOAc, 1:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of dibenzo[b,f][1,4]oxazepin-11(10H)-one (0.623 g, 2.95 mmol) in THF (10.0 mL), dichloromethane (10.0 mL) and triethylamine (2.0 mL, 14.7 mmol) was added diacetoxycopper (0.587 g, 3.25 mmol) followed by 4-(ethoxycarbonyl)phenylboronic acid (1.15 g, 5.91 mmol). The reaction mixture was stirred at room temperature for 5 days. It was diluted with ethyl acetate and this organic layer was washed with 10% HCl (2 times), water and brine, dried over sodium sulfate, filtered and evaporated. The crude was purified by flash chromatography (a 1st one with 20% ethyl acetate in hexanes and second one with 0.5% methanol in dichloromethane) to afford title compound 465 (248 mg, 23%) as a white solid. MS (m/z): 360.3 (M+H). this organic layer was washed with 10% HCl (2 times), water and brine dried over sodium sulfate filtered evaporated The crude was purified by flash chromatography (a 1st one with 20% ethyl acetate in hexanes and second one with 0.5% methanol in dichloromethane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using Procedure H-3 (Table 5) with dibenzo[b,f][1,4]oxazepin-11(10H)-one and 3-bromoprop-1-yne the title compound 85 was obtained (1.58 g, 89%) as an off-white solid. 1H NMR (DMSO-d6) δ (ppm): 7.76 (ddd, J=7.5, 1.7, 0.4 Hz, 1H), 7.65 (dd, J=8.0, 1.7 Hz, 1H), 7.61 (ddd, J=8.2, 7.2, 1.8 Hz, 1H), 7.41 (dd, J=7.8, 1.6 Hz, 1H), 7.37 (ddd, J=8.2, 1.0, 0.4 Hz, 1H), 7.34-7.24 (m, 3H), 4.83 (d, J=2.3 Hz, 2H), 3.31 (t, J=2.3 Hz, 1H). MS (m/z): 250.0 (M+H) was obtained (1.58 g, 89%) as an off-white solid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Using Procedure H-3 (Table 5) with dibenzo[b,f][1,4]oxazepin-11(10H)-one and 3-bromoprop-1-yne the title compound 85 was obtained (1.58 g, 89%) as an off-white solid. 1H NMR (DMSO-d6) δ (ppm): 7.76 (ddd, J=7.5, 1.7, 0.4 Hz, 1H), 7.65 (dd, J=8.0, 1.7 Hz, 1H), 7.61 (ddd, J=8.2, 7.2, 1.8 Hz, 1H), 7.41 (dd, J=7.8, 1.6 Hz, 1H), 7.37 (ddd, J=8.2, 1.0, 0.4 Hz, 1H), 7.34-7.24 (m, 3H), 4.83 (d, J=2.3 Hz, 2H), 3.31 (t, J=2.3 Hz, 1H). MS (m/z): 250.0 (M+H) was obtained (1.58 g, 89%) as an off-white solid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dibenzo[b,f][1,4]oxazepin-11(10H)-one (1.001 g, 4.7 mmol) was dissolved in THF (20 mL) and the borane (2M in THF, 20 mL, 40.0 mmol) was added. The reaction mixture was refluxed for 3 hours. The mixture was cooled down to room temperature and an excess of ethanol was added to quench the reaction. The resulting mixture was refluxed for 2 hours. The mixture was cooled down and concentrated in vacuo. The residue was dissolved in ethyl acetate and the organic layer was washed with water and brine, dried over sodium sulfate, filtered and evaporated to afford title compound 398 (0.945 g, quantitative). MS (m/z): 198.1 (M+H). 1H NMR (CD3OD) δ (ppm): 7.29-7.19 (m, 2H), 7.16-7.04 (m, 2H), 7.01-6.99 (m, 1H), 6.82-6.78 (m, 1H), 6.63-6.59 (m, 2H), 4.88 (s, 1H), 4.39 (s, 2H). MS (m/z): 198.1 (M+H). The reaction mixture was refluxed for 3 hours to quench the reaction The resulting mixture was refluxed for 2 hours The mixture was cooled down concentrated in vacuo The residue was dissolved in ethyl acetate the organic layer was washed with water and brine dried over sodium sulfate filtered evaporated