tert-butyl N-[(3S)-4-oxo-3,5-dihydro-2H-1,5-benzoxazepin-3-yl]carbamate

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

实验步骤: In 30 ml of 5N hydrogen chloride-ethyl acetate solution is dissolved 5 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one, and the mixture is allowed to stand at room temperature for 3 hours. The deposited crystals are collected by filtration to give 3.8 g of 3(S)-amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one hydrochloride as a colorless needles, melting at 230°-240° C. (decomposition). The deposited crystals are collected by filtration

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

实验步骤: In 30 ml of 5N hydrogen chloride-ethyl acetate solution is dissolved 5 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one, and the mixture is allowed to stand at room temperature for 3 hours. The deposited crystals are collected by filtration to give 3.8 g of 3(S)-amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one hydrochloride as a colorless needles, melting at 230°-240° C. (decomposition). The deposited crystals are collected by filtration

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

实验步骤: In 150 ml of N,N-dimethylformamide is dissolved 12.3 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one, and 8.7 g of benzyl chloroacetate, 8.7 g of anhydrous potassium carbonate and 1 g of potassium iodide are added to the solution. After stirring for 15 hours, the mixture is poured in ice-cooled water. The deposited material is collected by filtration, washed with water and recrystallized from ethyl acetate-hexane to give 11.7 g of benzyl 3(S)-tert-butoxycarbonylamino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate as colorless prisms, melting at 122°-124° C. are added to the solution the mixture is poured in ice- The deposited material is collected by filtration washed with water recrystallized from ethyl acetate-hexane

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

实验步骤: In 150 ml of N,N-dimethylformamide is dissolved 12.3 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one, and 8.7 g of benzyl chloroacetate, 8.7 g of anhydrous potassium carbonate and 1 g of potassium iodide are added to the solution. After stirring for 15 hours, the mixture is poured in ice-cooled water. The deposited material is collected by filtration, washed with water and recrystallized from ethyl acetate-hexane to give 11.7 g of benzyl 3(S)-tert-butoxycarbonylamino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate as colorless prisms, melting at 122°-124° C. are added to the solution the mixture is poured in ice- The deposited material is collected by filtration washed with water recrystallized from ethyl acetate-hexane

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

实验步骤: In 120 ml of N,N-dimethylformamide is dissolved 21.4 g of O-(o-aminophenyl)-Boc-L-serine obtained in Example 2, and 14 g of diethyl phosphorocyanidate is added dropwise to the solution with stirring at ice bath temperature. The mixture is stirred for 10 minutes, and 7 g of triethylamine is added dropwise to the mixture. After stirring for 1 hour, the mixture is poured in ice-cooled water. The deposited material is collected by filtration, washed with water, dried and recrystallized from ethyl acetate-hexane to give 12.3 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one as colorless plates, melting at 202°-203° C. is added dropwise to the solution The mixture is stirred for 10 minutes After stirring for 1 hour the mixture is poured in ice- The deposited material is collected by filtration washed with water dried recrystallized from ethyl acetate-hexane

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

实验步骤: In 120 ml of N,N-dimethylformamide is dissolved 21.4 g of O-(o-aminophenyl)-Boc-L-serine obtained in Example 2, and 14 g of diethyl phosphorocyanidate is added dropwise to the solution with stirring at ice bath temperature. The mixture is stirred for 10 minutes, and 7 g of triethylamine is added dropwise to the mixture. After stirring for 1 hour, the mixture is poured in ice-cooled water. The deposited material is collected by filtration, washed with water, dried and recrystallized from ethyl acetate-hexane to give 12.3 g of 3(S)-tert-butoxycarbonylamino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one as colorless plates, melting at 202°-203° C. is added dropwise to the solution The mixture is stirred for 10 minutes After stirring for 1 hour the mixture is poured in ice- The deposited material is collected by filtration washed with water dried recrystallized from ethyl acetate-hexane

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

实验步骤: A mixture of (S)-tert-butyl 4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate (1.412 g, 5.07 mmol), 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (1.59 g, 5.58 mmol), Cs2CO3 (1.98 g, 6.09 mmol), and NaI (913 mg, 6.09 mmol) in DMF (16.9 mL) was stirred at RT for 22 h, diluted with H2O and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and. The filtrate was concentrated to give a residue that was purified by silica gel chromatography to give (S)-tert-butyl 5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate (1.804 g, 67%) as an off-white solid. MS m/z 549/551 (MNa)+ extracted with EtOAc The combined extracts were washed with brine dried over Na2SO4 The filtrate was concentrated to give a residue that was purified by silica gel chromatography

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

实验步骤: 1 M lithium bis(trimethylsilyl) amide in THF (3.07 mL, 1 eq) was added to a solution of ((S)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-carbamic acid-t-butyl ester (855 mg, 3.07 mmol, 1.0 eq) in THF (10 mL) at −78° C. After 30 min. 1-(chloromethyl)-2-methylnaphthalene (586 mg, 3.07 mmol, 1 eq) and NaI (461 mg, 3.07 mmol, 1 eq) were added and the mixture warmed to RT over 2 h. The solvent was removed and the residue was suspened in EtOAc and washed with H2O. The aqueous extracts were extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by silica chromatography to afford (S)-tert-butyl 5-((2-methylnaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate (1.01 g, 75%) as a yellow foam. The solvent was removed washed with H2O The aqueous extracts were extracted with EtOAc the combined organic layers were dried over Na2SO4 filtered concentrated The residue was purified by silica chromatography

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

实验步骤: 1 M lithium bis(trimethylsilyl) amide in THF (3.07 mL, 1 eq) was added to a solution of ((S)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-carbamic acid-t-butyl ester (855 mg, 3.07 mmol, 1.0 eq) in THF (10 mL) at −78° C. After 30 min. 1-(chloromethyl)-2-methylnaphthalene (586 mg, 3.07 mmol, 1 eq) and NaI (461 mg, 3.07 mmol, 1 eq) were added and the mixture warmed to RT over 2 h. The solvent was removed and the residue was suspened in EtOAc and washed with H2O. The aqueous extracts were extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered and concentrated. The residue was purified by silica chromatography to afford (S)-tert-butyl 5-((2-methylnaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate (1.01 g, 75%) as a yellow foam. The solvent was removed washed with H2O The aqueous extracts were extracted with EtOAc the combined organic layers were dried over Na2SO4 filtered concentrated The residue was purified by silica chromatography

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

实验步骤: In a similar manner to that described for the preparation of (S)-tert-butyl 4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate except the crude product was purified by silica gel chromatography, (S)-3-(2-amino-6-(methoxycarbonyl)phenoxy)-2-(tert-butoxycarbonylamino)propanoic acid (1.5 g, 4.83 mmol) was converted to the title compound (0.65 g, 46%) as a white solid.

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

实验步骤: In a similar manner to that described for the preparation of (S)-tert-butyl 4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate except the crude product was purified by silica gel chromatography, (S)-3-(2-amino-6-(methoxycarbonyl)phenoxy)-2-(tert-butoxycarbonylamino)propanoic acid (3.9 g, 6.6 mmol) was converted to the title compound (1.46 g, 65%) as a white foam.

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

实验步骤: In a similar manner to that described for the preparation of (S)-tert-butyl 4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylcarbamate except the crude product was purified by silica gel chromatography, (S)-3-(2-amino-6-(methoxycarbonyl)phenoxy)-2-(tert-butoxycarbonylamino)propanoic acid (3.9 g, 6.6 mmol) was converted to the title compound (1.46 g, 65%) as a white foam.