benzyl N-(7-aminoheptyl)carbamate

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

実験手順: To the solution of 21 (350 mg, 1.324 mmol) in THF (4 mL) was added diglycolic anhydride (161 mg, 1.39 mmol) in one portion. The resultant mixture was stirred at ambient temperature for 12 h. After removed THF under reduced pressure, the residue was crystallized by EtOAc/hexane to give 429 mg white solid as first crop, in 85% yield. 1H NMR (400 MHz, DMSO-d6): δ12.79 (brs, 1H), 7.81 (t, J=5.52 Hz, 1H), 7.34-7.29 (m, 5H), 7.21 (t, J=5.46 Hz, 1H), 5.00 (s, 2H), 4.10 (s, 2H), 3.94 (s, 2H), 3.08 (q, J=6.56 Hz, 2H), 2.97 (q, J=6.28 Hz, 2H), 1.42-1.37 (m, 4H), 1.24 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 171.43, 168.53, 156.06, 137.30, 128.27, 127.65, 70.18, 67.88, 65.04, 40.22, 38.08, 29.65, 29.00, 28.38, 26.28, 26.14. mp 74-74.5° C. IR v (Diamond, cm−1): 3374, 3331, 1726, 1688, 1608, 1548, 1249, 1236, 1135, 956, 701. MS (ESI) m/z found 381.4 (M+H)+. After removed THF under reduced pressure the residue was crystallized by EtOAc/hexane

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

実験手順: To the solution of 21 (350 mg, 1.324 mmol) in THF (4 mL) was added diglycolic anhydride (161 mg, 1.39 mmol) in one portion. The resultant mixture was stirred at ambient temperature for 12 h. After removed THF under reduced pressure, the residue was crystallized by EtOAc/hexane to give 429 mg white solid as first crop, in 85% yield. 1H NMR (400 MHz, DMSO-d6): δ12.79 (brs, 1H), 7.81 (t, J=5.52 Hz, 1H), 7.34-7.29 (m, 5H), 7.21 (t, J=5.46 Hz, 1H), 5.00 (s, 2H), 4.10 (s, 2H), 3.94 (s, 2H), 3.08 (q, J=6.56 Hz, 2H), 2.97 (q, J=6.28 Hz, 2H), 1.42-1.37 (m, 4H), 1.24 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 171.43, 168.53, 156.06, 137.30, 128.27, 127.65, 70.18, 67.88, 65.04, 40.22, 38.08, 29.65, 29.00, 28.38, 26.28, 26.14. mp 74-74.5° C. IR v (Diamond, cm−1): 3374, 3331, 1726, 1688, 1608, 1548, 1249, 1236, 1135, 956, 701. MS (ESI) m/z found 381.4 (M+H)+. After removed THF under reduced pressure the residue was crystallized by EtOAc/hexane

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

実験手順: On an ice-water bath, to the solution of 1,7-diaminoheptane (1.433 g, 11 mmol) in CH2Cl2/MeOH (125 mL/125 mL) was added the solution of CbzCl (1.71 g, 10 mmol) in CH2Cl2 (250 mL) dropwise within 12 h while keeping the temperature below 5° C. The mixture was allowed to stir at the same temperature for another half of an hour before concentrated under reduced pressure to remove most of the MeOH. Water (150 mL) was then added, and the aqueous layer was adjusted to pH=2 using 6 N HCl. The layers were separated. The aqueous layer was washed with DCM (50 mL×3), then adjusted to pH=12 with 10 N NaOH and extracted with DCM (50 mL×3). The combined organic layers were dried over Na2SO4, concentrated and purified by flash column using DCM/MeOH (9/1) to give 856 mg white solid in 32% yield. 1H NMR (400 MHz, CDCl3): δ7.35-7.29 (m, 5H), 5.09 (s, 2H), 4.73 (brs, 1H), 3.18 (q, J=6.64 Hz, 2H), 2.67 (t, J=6.94 Hz, 2H), 1.55-1.44 (m, 2H), 1.44-1.40 (m, 2H), 1.32 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 156.40, 136.70, 128.50, 128.09, 128.06, 66.55, 42.18, 41.06, 33.71, 29.91, 29.09, 26.76, 26.68. mp 78-80° C. IR v (Diamond, cm−1): 3327, 1686, 1532, 1263, 1144. MS (ESI) m/z found 264.8 (M+H)+. the temperature below 5° C before concentrated under reduced pressure to remove most of the MeOH Water (150 mL) was then added The layers were separated The aqueous layer was washed with DCM (50 mL×3) extracted with DCM (50 mL×3) The combined organic layers were dried over Na2SO4 concentrated purified by flash column

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

実験手順: To the solution of 21 (350 mg, 1.324 mmol) in THF (4 mL) was added diglycolic anhydride (161 mg, 1.39 mmol) in one portion. The resultant mixture was stirred at ambient temperature for 12 h. After removed THF under reduced pressure, the residue was crystallized by EtOAc/hexane to give 429 mg white solid as first crop, in 85% yield. 1H NMR (400 MHz, DMSO-d6): δ12.79 (brs, 1H), 7.81 (t, J=5.52 Hz, 1H), 7.34-7.29 (m, 5H), 7.21 (t, J=5.46 Hz, 1H), 5.00 (s, 2H), 4.10 (s, 2H), 3.94 (s, 2H), 3.08 (q, J=6.56 Hz, 2H), 2.97 (q, J=6.28 Hz, 2H), 1.42-1.37 (m, 4H), 1.24 (m, 6H). 13C NMR (100 MHz, CDCl3): 171.43, 168.53, 156.06, 137.30, 128.27, 127.65, 70.18, 67.88, 65.04, 40.22, 38.08, 29.65, 29.00, 28.38, 26.28, 26.14. mp 74-74.5° C. IR v (Diamond, cm−1): 3374, 3331, 1726, 1688, 1608, 1548, 1249, 1236, 1135, 956, 701. MS (ESI) found 381.4 (M+H)+. After removed THF under reduced pressure the residue was crystallized by EtOAc/hexane

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

実験手順: On an ice-water bath, to the solution of 1,7-diaminoheptane (1.433 g, 11 mmol) in CH2Cl2/MeOH (125 mL/125 mL) was added the solution of CbzCl (1.71 g, 10 mmol) in CH2Cl2 (250 mL) dropwise within 12 h while keeping the temperature below 5° C. The mixture was allowed to stir at the same temperature for another half of an hour before concentrated under reduced pressure to remove most of the MeOH. Water (150 mL) was then added, and the aqueous layer was adjusted to pH=2 using 6 N HCl. The layers were separated. The aqueous layer was washed with DCM (50 mL×3), then adjusted to pH=12 with 10 N NaOH and extracted with DCM (50 mL×3). The combined organic layers were dried over Na2SO4, concentrated and purified by flash column using DCM/MeOH (9/1) to give 856 mg white solid in 32% yield. 1H NMR (400 MHz, CDCl3): δ 7.35-7.29 (m, 5H), 5.09 (s, 2H), 4.73 (brs, 1H), 3.18 (q, J=6.64 Hz, 2H), 2.67 (t, J=6.94 Hz, 2H), 1.55-1.44 (m, 2H), 1.44-0 (m, 2H), 1.32 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 156.40, 136.70, 128.50, 128.09, 128.06, 66.55, 42.18, 41.06, 33.71, 29.91, 29.09, 26.76, 26.68. mp 78-80° C. IR v (Diamond, cm−1): 3327, 1686, 1532, 1263, 1144. MS (ESI) found 264.8 (M+H)+. the temperature below 5° C before concentrated under reduced pressure to remove most of the MeOH Water (150 mL) was then added The layers were separated The aqueous layer was washed with DCM (50 mL×3) extracted with DCM (50 mL×3) The combined organic layers were dried over Na2SO4 concentrated purified by flash column

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

実験手順: In 80 ml of the tetrahydrofuran were dissolved 1.00 g of DL-trans-benzylhydrogenepoxysuccinate, 1.70 g of N-L-leucyl-N'-benzyloxycarbonyl-1,7-diaminoheptane, 0.73 g of 1-hydroxybenzotriazole and 0.55 g of N-methylmorpholine. To the solution was slowly added 0.95 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride under ice-cooling with stirring. The mixture was stirred for 2 hours under ice-cooling and then for 2 hours at room temperature. The solution was concentrated under reduced pressure and admixed with 100 ml of ethyl acetate and 100 ml of water and the mixture was shaken vigorously. The ethyl acetate layer was separated and washed successively with a 10% aqueous hydrochloric acid solution, an aqueous saturated bicarbonate solution and an aqueous saturated sodium chloride solution and concentrated to dryness. The resulting residue was purified by column chromatography on silica gel (chloroform:acetone=10:1) and recrystallized from ethyl acetate-n-hexane to give 1.50 g of N-[N-DL-3-trans-benzyloxycarboxyloxirane-2-carbonyl)-L-leucyl]-N'-benzyloxycarbonyl-1,7-diaminoheptane m.p. 134° C. Yield: 67%. cooling The mixture was stirred for 2 hours under ice- cooling The solution was concentrated under reduced pressure the mixture was shaken vigorously The ethyl acetate layer was separated washed successively with a 10% aqueous hydrochloric acid solution an aqueous saturated bicarbonate solution and an aqueous saturated sodium chloride solution and concentrated to dryness The resulting residue was purified by column chromatography on silica gel (chloroform:acetone=10:1) recrystallized from ethyl acetate-n-hexane

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

実験手順: To the solution of 21 (350 mg, 1.324 mmol) in THF (4 mL) was added diglycolic anhydride (161 mg, 1.39 mmol) in one portion. The resultant mixture was stirred at ambient temperature for 12 h. After removed THF under reduced pressure, the residue was crystallized by EtOAc/hexane to give 429 mg white solid as first crop, in 85% yield. 1H NMR (400 MHz, DMSO-d6): δ12.79 (brs, 1H), 7.81 (t, J=5.52 Hz, 1H), 7.34-7.29 (m, 5H), 7.21 (t, J=5.46 Hz, 1H), 5.00 (s, 2H), 4.10 (s, 2H), 3.94 (s, 2H), 3.08 (q, J=6.56 Hz, 2H), 2.97 (q, J=6.28 Hz, 2H), 1.42-1.37 (m, 4H), 1.24 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 171.43, 168.53, 156.06, 137.30, 128.27, 127.65, 70.18, 67.88, 65.04, 40.22, 38.08, 29.65, 29.00, 28.38, 26.28, 26.14. mp 74-74.5° C. IR v (Diamond, cm−1): 3374, 3331, 1726, 1688, 1608, 1548, 1249, 1236, 1135, 956, 701. MS (ESI) m/z found 381.4 (M+H)+. After removed THF under reduced pressure the residue was crystallized by EtOAc/hexane

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

実験手順: On an ice-water bath, to the solution of 1,7-diaminoheptane (1.433 g, 11 mmol) in CH2Cl2/MeOH (125 mL/125 mL) was added the solution of CbzCl (1.71 g, 10 mmol) in CH2Cl2 (250 mL) dropwise within 12 h while keeping the temperature below 5° C. The mixture was allowed to stir at the same temperature for another half of an hour before concentrated under reduced pressure to remove most of the MeOH. Water (150 mL) was then added, and the aqueous layer was adjusted to pH=2 using 6 N HCl. The layers were separated. The aqueous layer was washed with DCM (50 mL×3), then adjusted to pH=12 with 10 N NaOH and extracted with DCM (50 mL×3). The combined organic layers were dried over Na2SO4, concentrated and purified by flash column using DCM/MeOH (9/1) to give 856 mg white solid in 32% yield. 1H NMR (400 MHz, CDCl3): δ7.35-7.29 (m, 5H), 5.09 (s, 2H), 4.73 (brs, 1H), 3.18 (q, J=6.64 Hz, 2H), 2.67 (t, J=6.94 Hz, 2H), 1.55-1.44 (m, 2H), 1.44-1.40 (m, 2H), 1.32 (m, 6H). 13C NMR (100 MHz, CDCl3): δ 156.40, 136.70, 128.50, 128.09, 128.06, 66.55, 42.18, 41.06, 33.71, 29.91, 29.09, 26.76, 26.68. mp 78-80° C. IR v (Diamond, cm−1): 3327, 1686, 1532, 1263, 1144. MS (ESI) m/z found 264.8 (M+H)+. the temperature below 5° C before concentrated under reduced pressure to remove most of the MeOH Water (150 mL) was then added The layers were separated The aqueous layer was washed with DCM (50 mL×3) extracted with DCM (50 mL×3) The combined organic layers were dried over Na2SO4 concentrated purified by flash column