(2,3,5,6-tetrafluorophenyl) 2,2,2-trifluoroacetate

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2,3,5,6-Tetrafluorophenyl trifluoroacetate (2.6 g, 10 mmol, H. B. Gamper, M. W. Reed, T. Cox, J. S. Virosco, A. D. Adams, A. A. Gall, J. K. Scholler and R. B. Meyer,Jr. Nucleic Acids Res., 1993, Vol. 21, No.1, 145-150) was added dropwise to a solution of 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylic acid (1.4 g, 6.1 mmol, D. L. Boger, R. S. Coleman, and B. J. Invergo. J.Orq.Chem., 1987, Vol.52, 1521-1530) and triethylamine (1.4 ml, 10 mmol) in 15 ml of anhydrous DMF. After 1 hr, the reaction mixture was concentrated under vacuum (0.2 mm). The residue was triturated with 2 ml of dry dichloromethane. Ethyl ether (50 ml) was added and the mixture was left at 0° C. overnight. The precipitate was collected by filtration on sintered glass funnel, washed first with 50% ether/CH2Cl2 (10 ml), then with ether (50 ml) and dried in vacuo. The product was obtained as a yellow solid (1.8 g, 75%): 1H NMR (Me2SO-d6, 200 MHz, ppm) 12.32 (s, 1H, NH), 8.13 (d, 1H, J=9 Hz, C4-H), 8.01 (m, 1H, C6F4H), 7.41 (s, 1H, C8-H), 7.26 (d, 1H, J=9 Hz, C5-H), 6.17 (s, 2H, CONH2), 3.99 (t, 2H, J=9 Hz, NCH2CH2), 3.30 (t, 2H, J=9 Hz, NCH2CH2). Anal. Calcd. for C18H11N3O3F4×2H2O: C, 50.3; H, 3.52; N, 9.7. Found; C, 50.81; H, 3.60; N, 9.95. the reaction mixture was concentrated under vacuum (0.2 mm) The residue was triturated with 2 ml of dry dichloromethane Ethyl ether (50 ml) was added the mixture was left at 0° C. overnight The precipitate was collected by filtration on sintered glass funnel washed first with 50% ether/CH2Cl2 (10 ml) with ether (50 ml) and dried in vacuo

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

実験手順: 2,3,5,6-Tetrafluorophenyl trifluoroacetate (2.6 g, 10 mmol, H. B. Gamper, M. W. Reed, T. Cox, J. S. Virosco, A. D. Adams, A. A. Gall, J. K. Scholler and R. B. Meyer,Jr. Nucleic Acids Res., 1993, Vol. 21, No.1, 145-150) was added dropwise to a solution of 3-carbamoyl-1,2-dihydro-3H-pyrrolo[3,2-e]indole-7-carboxylic acid (1.4 g, 6.1 mmol, D. L. Boger, R. S. Coleman, and B. J. Invergo. J.Orq.Chem., 1987, Vol.52, 1521-1530) and triethylamine (1.4 ml, 10 mmol) in 15 ml of anhydrous DMF. After 1 hr, the reaction mixture was concentrated under vacuum (0.2 mm). The residue was triturated with 2 ml of dry dichloromethane. Ethyl ether (50 ml) was added and the mixture was left at 0° C. overnight. The precipitate was collected by filtration on sintered glass funnel, washed first with 50% ether/CH2Cl2 (10 ml), then with ether (50 ml) and dried in vacuo. The product was obtained as a yellow solid (1.8 g, 75%): 1H NMR (Me2SO-d6, 200 MHz, ppm) 12.32 (s, 1H, NH), 8.13 (d, 1H, J=9 Hz, C4-H), 8.01 (m, 1H, C6F4H), 7.41 (s, 1H, C8-H), 7.26 (d, 1H, J=9 Hz, C5-H), 6.17 (s, 2H, CONH2), 3.99 (t, 2H, J=9 Hz, NCH2CH2), 3.30 (t, 2H, J=9 Hz, NCH2CH2). Anal. Calcd. for C18H11N3O3F4×2H2O: C, 50.3; H, 3.52; N, 9.7. Found; C, 50.81; H, 3.60; N, 9.95. the reaction mixture was concentrated under vacuum (0.2 mm) The residue was triturated with 2 ml of dry dichloromethane Ethyl ether (50 ml) was added the mixture was left at 0° C. overnight The precipitate was collected by filtration on sintered glass funnel washed first with 50% ether/CH2Cl2 (10 ml) with ether (50 ml) and dried in vacuo

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

実験手順: The acid 6 obtained as described above (2.2 g, 4.4 mmol) was dissolved in anhydrous CH2Cl2 and treated with 1 ml of triethylamine followed by 0.8 ml of 2,3,5,6-tetrafluorophenyltrifluoroacetate. After being kept at room temperature for 30 min, the reaction was concentrated to an oil (crude 7), which then was re-suspended in 20% ethyl acetate/80%hexane and applied to a silica gel column. Elution with 15% ethyl acetate/85% hexane and concentration of the pure product fractions afforded 2.0 g (82%) of the TFP ester (7) as a colorless, viscous oil. the reaction was concentrated to an oil (crude 7), which Elution with 15% ethyl acetate/85% hexane and concentration of the pure product fractions

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

実験手順: A 2.5 g (10.3 mmol) quantity of d-biotin in 20 mL anhydrous DMF under argon atmosphere was warmed to 60° C. with stirring to effect dissolution. 1.7 mL (12.5 mmol) triethylamine was added, followed by 3.4 g (12.5 mmol) 1. The mixture was stirred for 2 hours, after which the solvent was removed by rotary evaporation. The resultant semi-solid was triturated with 15 mL ether twice to produce a white solid (2.6 g, 65%). 1H-NMR. (Ref. Wilbur, D. S., Bioconj. Chem., v8 pp572-584) dissolution The mixture was stirred for 2 hours after which the solvent was removed by rotary evaporation The resultant semi-solid was triturated with 15 mL ether twice

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

実験手順: 2,3,5,6-Tetrafluorophenyl trifluoroacetate (1.7 g, 6.5 mmol) was added dropwise to a solution of FMOC-alanine (2.0 g, 6.4 mmol) and triethylamine (1.0 ml, 7 mmol) in 20 ml of anhydrous CH2Cl2. After 1 hr., CH2Cl2 was removed by evaporation at reduced pressure using rotary evaporator, redissolved in 30 ml ethylacetate/hexane (1:1). Flash chromatography (4×20 cm, hexane/ethyl acetate, 3:1) afforded rude 4 as a white solid. It was recrystallized from hexane/ethyl acetate to give 4 as a white crystalline solid (2.3 g, 78%): 1H NMR (CDCl3, 200 MHz, ppm) 7.73 (d, 2H, J=7.1 Hz, aromatic protons), 7.75 (d, 2H, J=7.7 Hz, aromatic protons), 7.24-7.42 (m, 411, aromatic protons), 7.01 (m, 1H, C6F4H), 5.21 (br s, 1H, —CONH—), 4.38 (d, 2H, J=7.1 Hz, —CH2OCO—), 4.20 (m, 1H, benzyl proton), 3.58 (m, −2H, NCH 2), 2.93 (t, 2H, J=5.4 Hz, —CH2CO—). Anal. Calcd. for C24H17NO4F4: C, 62.75; H, 3.73; N, 3.05. Found: C, 62.52; H, 3.59; N, 3.01. , CH2Cl2 was removed by evaporation at reduced pressure evaporator redissolved in 30 ml ethylacetate/hexane (1:1)

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

実験手順: 2,3,5,6-Tetrafluorophenyl trifluoroacetate (1.7 g, 6.5 mmol) was added dropwise to a solution of FMOC-alanine (2.0 g, 6.4 mmol) and triethylamine (1.0 ml, 7 mmol) in 20 ml of anhydrous CH2Cl2. After 1 hr., CH2Cl2 was removed by evaporation at reduced pressure using rotary evaporator, redissolved in 30 ml ethylacetate/hexane (1:1). Flash chromatography (4×20 cm, hexane/ethyl acetate, 3:1) afforded rude 4 as a white solid. It was recrystallized from hexane/ethyl acetate to give 4 as a white crystalline solid (2.3 g, 78%): 1H NMR (CDCl3, 200 MHz, ppm) 7.73 (d, 2H, J=7.1 Hz, aromatic protons), 7.75 (d, 2H, J=7.7 Hz, aromatic protons), 7.24-7.42 (m, 411, aromatic protons), 7.01 (m, 1H, C6F4H), 5.21 (br s, 1H, —CONH—), 4.38 (d, 2H, J=7.1 Hz, —CH2OCO—), 4.20 (m, 1H, benzyl proton), 3.58 (m, −2H, NCH 2), 2.93 (t, 2H, J=5.4 Hz, —CH2CO—). Anal. Calcd. for C24H17NO4F4: C, 62.75; H, 3.73; N, 3.05. Found: C, 62.52; H, 3.59; N, 3.01. , CH2Cl2 was removed by evaporation at reduced pressure evaporator redissolved in 30 ml ethylacetate/hexane (1:1)

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

実験手順: 2,3,5,6-Tetrafluorophenyl trifluoroacetate (1.7 g, 6.5 mmol) was added dropwise to a solution of FMOC-alanine (2.0 g, 6.4 mmol) and triethylamine (1.0 ml, 7 mmol) in 20 ml of anhydrous CH2Cl2. After 1 hr., CH2Cl2 was removed by evaporation at reduced pressure using rotary evaporator, redissolved in 30 ml ethylacetate/hexane (1:1). Flash chromatography (4×20 cm, hexane/ethyl acetate, 3:1) afforded rude 4 as a white solid. It was recrystallized from hexane/ethyl acetate to give 4 as a white crystalline solid (2.3 g, 78%): 1H NMR (CDCl3, 200 MHz, ppm) 7.73 (d, 2H, J=7.1 Hz, aromatic protons), 7.75 (d, 2H, J=7.7 Hz, aromatic protons), 7.24-7.42 (m, 4H, aromatic protons), 7.01 (m, 1H, C6F4H), 5.21 (br s, 1H, —CONH—), 4.38 (d, 2H, J=7.1 Hz, —CH2OCO—), 4.20 (m, 1H, benzyl proton), 3.58 (m, -2H, NCH 2), 2.93 (t, 2H, J=5.4 Hz, —CH2CO—). Anal. Calcd. for C24H17NO4F4: C, 62.75; H, 3.73; N, 3.05. Found: C, 62.52; H, 3.59; N, 3.01. , CH2Cl2 was removed by evaporation at reduced pressure evaporator redissolved in 30 ml ethylacetate/hexane (1:1)

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

実験手順: Trifluoroacetic anhydride (28 mL, 0.2 mol) was added dropwise with stirring to 27.1 g (0,163 mol) of 2,3,5,6tetrafluorophenol. Boron trifluoride etherate (0.2 mL) was added and the mixture was refluxed overnight. The residual solution was distilled at atmospheric pressure to remove trifluoroacetic anhydride and trifluoroacetic acid. The desired product 18 (32.2 g; 75% yield) was collected at 45° C. (18mm) as a colorless liquid: the mixture was refluxed overnight The residual solution was distilled at atmospheric pressure to remove trifluoroacetic anhydride and trifluoroacetic acid

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

実験手順: 2,3,5,6-Tetrafluorophenyl trifluoroacetate (1.7 g, 6.5 mmol) was added dropwise to a solution of FMOC-alanine (2.0 g, 6.4 mmol) and triethylamine (1.0 ml, 7 mmol) in 20 ml of anhydrous CH2Cl2. After 1 hr., CH2Cl2 was removed by evaporation at reduced pressure using rotary evaporator, redissolved in 30 ml ethylacetate/hexane (1:1). Flash chromatography (4×20 cm, hexane/ethyl acetate, 3:1) afforded rude 4 as a white solid. It was recrystallized from hexane/ethyl acetate to give 4 as a white crystalline solid (2.3 g, 78%): 1H NMR (CDCl3, 200 MHz, ppm) 7.73 (d, 2H, J=7.1 Hz, aromatic protons), 7.75 (d, 2H, J=7.7 Hz, aromatic protons), 7.24-7.42 (m, 4H, aromatic protons), 7.01 (m, 1H, C6F4H), 5.21 (br s, 1H, —CONH—), 4.38 (d, 2H, J=7.1 Hz, —CH2OCO—), 4.20 (m, 1H, benzyl proton), 3.58 (m, -2H, NCH 2), 2.93 (t, 2H, J=5.4 Hz, —CH2CO—). Anal. Calcd. for C24H17NO4F4: C, 62.75; H, 3.73; N, 3.05. Found: C, 62.52; H, 3.59; N, 3.01. , CH2Cl2 was removed by evaporation at reduced pressure evaporator redissolved in 30 ml ethylacetate/hexane (1:1)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Trifluoroacetic anhydride (28 mL, 0.2 mol) was added dropwise with stirring to 27.1 g (0,163 mol) of 2,3,5,6tetrafluorophenol. Boron trifluoride etherate (0.2 mL) was added and the mixture was refluxed overnight. The residual solution was distilled at atmospheric pressure to remove trifluoroacetic anhydride and trifluoroacetic acid. The desired product 18 (32.2 g; 75% yield) was collected at 45° C. (18mm) as a colorless liquid: the mixture was refluxed overnight The residual solution was distilled at atmospheric pressure to remove trifluoroacetic anhydride and trifluoroacetic acid