O-(2-叠氮乙基)七聚乙二醇

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: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-yne) (960 mg, 2.52 mmol, 1 equiv.), triphenylphosphine (992 mg, 3.78 mmol, 1.5 equiv.), and water (68 μL, 3.78 mmol, 1.5 equiv.) were dissolved in THF (10 mL) and stirred for 12 h. Reaction was concentrated and chromatographed (3 cm×20 cm Silica, CH2Cl2 then ramp to 80:20:1 CH2Cl2:MeOH:Et3N) and concentrated to yield 3,6,9,12,15,18,21,24-octaoxaheptacos-26-yn-1-amine (9) as a clear oil (815 mg, 91% yield). IR (thin film, NaCl) 3105 (br), 2914 (m), 1781 (m), 1638 (m), 1169 (s) cm−1. 1H-NMR (500 MHz, CDCl3) δ 4.17 (d, 2H, J=2.4), 3.66-3.57 (m, 28H), 3.54 (t, 2H, J=5.3 Hz), 2.88 (t, 2H, J=5.0 Hz), 2.41 (t, 1H, J=2.4 Hz), 2.18 (br s, 2H). 13C NMR (125 MHz, CDCl3) δ 79.52, 74.59, 72.54, 70.41, 70.38, 70.38, 70.35, 70.31, 70.20, 70.06, 68.90, 58.20, 41.44. HRMS (ES+) calc'd for C19H37NO8 (M+H) m/z 408.259194. Found 408.25712. Reaction was concentrated chromatographed (3 cm×20 cm Silica, CH2Cl2 MeOH:Et3N) and concentrated

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

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-yne) (960 mg, 2.52 mmol, 1 equiv.), triphenylphosphine (992 mg, 3.78 mmol, 1.5 equiv.), and water (68 μL, 3.78 mmol, 1.5 equiv.) were dissolved in THF (10 mL) and stirred for 12 h. Reaction was concentrated and chromatographed (3 cm×20 cm Silica, CH2Cl2 then ramp to 80:20:1 CH2Cl2:MeOH:Et3N) and concentrated to yield 3,6,9,12,15,18,21,24-octaoxaheptacos-26-yn-1-amine (9) as a clear oil (815 mg, 91% yield). IR (thin film, NaCl) 3105 (br), 2914 (m), 1781 (m), 1638 (m), 1169 (s) cm−1. 1H-NMR (500 MHz, CDCl3) δ 4.17 (d, 2H, J=2.4), 3.66-3.57 (m, 28H), 3.54 (t, 2H, J=5.3 Hz), 2.88 (t, 2H, J=5.0 Hz), 2.41 (t, 1H, J=2.4 Hz), 2.18 (br s, 2H). 13C NMR (125 MHz, CDCl3) δ 79.52, 74.59, 72.54, 70.41, 70.38, 70.38, 70.35, 70.31, 70.20, 70.06, 68.90, 58.20, 41.44. HRMS (ES+) calc'd for C19H37NO8 (M+H) m/z 408.259194. Found 408.25712. Reaction was concentrated chromatographed (3 cm×20 cm Silica, CH2Cl2 MeOH:Et3N) and concentrated

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

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-ol) (1.1 g, 3.17 mmol, 1.0 equiv.) was dissolved in N,N′-dimethylformamide (6 mL), and sodium hydride (152 mg, 6.34 mmol, 2.0 equiv.) was added, followed by propargyl bromide (80% in PhMe, 683 μL, 6.34 mmol, 2.0 equiv.). The reaction ran for 4 h at rt, at which time it was found complete by NMR aliquot. The reaction was taken up in CH2Cl2 (25 mL) and washed with a saturated aqueous ammonium chloride solution (25 mL). The aqueous solution was back-extracted with dichloromethane (2×10 mL), and combined organics were dried over MgSO4 and concentrated to a brown oil. Chromatography (3 cm×20 cm Silica gel, 3% MeOH/CH2Cl2) yielded azido-PEG8-yne (960 mg, 78% yield). IR (thin film/NaCl) 2874 (m), 2110 (m), 1160 (s), 1105 (s) cm−1; 1HNMR (400 MHz, CDCl3) δ 4.20 (d, J=2.4 Hz, 2H), 3.58 (m, 30H), 3.39 (t, J=5.1 Hz, 2H), 2.43 (t, J=2.4 Hz, 1H), 1.82 (s, 1H); 13CNMR (125 MHz, CDCl3) δ 79.82, 74.72, 70.75, 7022, 68.27, 58.62, 50.84; HRMS (ES+) calc'd for C19H35N3O8 (M+Na) m/z 456.231637. Found 456.23182. washed with a saturated aqueous ammonium chloride solution (25 mL) The aqueous solution was back-extracted with dichloromethane (2×10 mL) combined organics were dried over MgSO4 concentrated to a brown oil

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (500 mg, 1.26 mmol) was dissolved in DCM (2 mL) and cooled to −10° C. DAST (482 μL, 3.78 mmol) was added in portions to the cooled solution and the resulting mixture was stirred at −10° C. for 30 minutes then allowed to warm to room temperature and stirred for additional 20 hours. The excess of DAST was quenched with methanol (5 mL) and the solvents were subsequently evaporated at the reduced pressure. The oily residue was dissolved in the water (3 mL) and the pH was adjusted to 5 using NaHCO3. The crude product was purified on semipreparative HPLC (System E) to yield 122 mg (24%) of 4 as a yellowish oil. 1H NMR (500 MHz, CDCl3): δ 3.39 (t, J=5.0 Hz, 2H), 3.65-3.68 (m, 26H), 3.75 (dt, J=4.2 Hz, 29.6 Hz, 2H), 4.56 (dt, J=4.0 Hz, 47.5 Hz, 2H); 13C NMR (125.7 MHz, CDCl3): δ 50.8, 70.1, 70.4, 70.5, 70.7-70.8, 70.9, 83.2 (d, J=169 Hz); 19F NMR (470.6 MHz, CDCl3): δ −225.9; MS ESI (m/z): [M+H]+ calcd. for C16H33FO7N3, 398.2. found 398.0. to warm to room temperature stirred for additional 20 hours The excess of DAST was quenched with methanol (5 mL) the solvents were subsequently evaporated at the reduced pressure The oily residue was dissolved in the water (3 mL) The crude product was purified on semipreparative HPLC (System E)

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

实验步骤: A solution of 23-azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (800 mg, 2.02 mmol) in pyridine (4 mL) was added dropwise to the solution of toluenesulfonyl chloride (771 mg, 4.04 mmol) and 4-dimethylaminopyridine (100 mg) in pyridine (10 mL) at room temperature. The mixture was stirred for 24 hours at room temperature. The solvent was evaporated and the crude product was purified on SiO2 column using hexanes/ethylacetate gradient 0-100% followed by ethylacetate/methanol gradient 0-100%, then purified on semipreparative HPLC (System E) to yield 280 mg (25%) of 3 as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 2.45 (s, 3H), 3.38 (t, J=5.02 Hz, 2H), 3.58-3.70 (m, 28H), 4.16 (t, J=5.00 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H); 13C NMR (100.6 MHz, CDCl3): δ 21.6, 50.7, 68.7, 69.2, 70.0, 70.5-70.8, 128.0, 129.7, 133.1, 144.7; MS ESI (m/z): [M+H]+ calcd. for C23H39N3O10S 549.24. found 549.9. The solvent was evaporated the crude product was purified on SiO2 column purified on semipreparative HPLC (System E)

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

实验步骤: A solution of 23-azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (800 mg, 2.02 mmol) in pyridine (4 mL) was added dropwise to the solution of toluenesulfonyl chloride (771 mg, 4.04 mmol) and 4-dimethylaminopyridine (100 mg) in pyridine (10 mL) at room temperature. The mixture was stirred for 24 hours at room temperature. The solvent was evaporated and the crude product was purified on SiO2 column using hexanes/ethylacetate gradient 0-100% followed by ethylacetate/methanol gradient 0-100%, then purified on semipreparative HPLC (System E) to yield 280 mg (25%) of 3 as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 2.45 (s, 3H), 3.38 (t, J=5.02 Hz, 2H), 3.58-3.70 (m, 28H), 4.16 (t, J=5.00 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.80 (d, J=8.4 Hz, 2H); 13C NMR (100.6 MHz, CDCl3): δ 21.6, 50.7, 68.7, 69.2, 70.0, 70.5-70.8, 128.0, 129.7, 133.1, 144.7; MS ESI (m/z): [M+H]+ calcd. for C23H39N3O10S 549.24. found 549.9. The solvent was evaporated the crude product was purified on SiO2 column purified on semipreparative HPLC (System E)

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

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-yne) (960 mg, 2.52 mmol, 1 equiv.), triphenylphosphine (992 mg, 3.78 mmol, 1.5 equiv.), and water (68 μL, 3.78 mmol, 1.5 equiv.) were dissolved in THF (10 mL) and stirred for 12 h. Reaction was concentrated and chromatographed (3 cm×20 cm Silica, CH2Cl2 then ramp to 80:20:1 CH2Cl2:MeOH:Et3N) and concentrated to yield 3,6,9,12,15,18,21,24-octaoxaheptacos-26-yn-1-amine (9) as a clear oil (815 mg, 91% yield). IR (thin film, NaCl) 3105 (br), 2914 (m), 1781 (m), 1638 (m), 1169 (s) cm−1. 1H-NMR (500 MHz, CDCl3) δ 4.17 (d, 2H, J=2.4), 3.66-3.57 (m, 28H), 3.54 (t, 2H, J=5.3 Hz), 2.88 (t, 2H, J=5.0 Hz), 2.41 (t, 1H, J=2.4 Hz), 2.18 (br s, 2H). 13C NMR (125 MHz, CDCl3) δ 79.52, 74.59, 72.54, 70.41, 70.38, 70.38, 70.35, 70.31, 70.20, 70.06, 68.90, 58.20, 41.44. HRMS (ES+) calc'd for C19H37NO8 (M+H) m/z 408.259194. Found 408.25712. Reaction was concentrated chromatographed (3 cm×20 cm Silica, CH2Cl2 MeOH:Et3N) and concentrated

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

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-ol) (1.1 g, 3.17 mmol, 1.0 equiv.) was dissolved in N,N′-dimethylformamide (6 mL), and sodium hydride (152 mg, 6.34 mmol, 2.0 equiv.) was added, followed by propargyl bromide (80% in PhMe, 683 μL 6.34 mmol, 2.0 equiv.). The reaction ran for 4 h at rt, at which time it was found complete by NMR aliquot. The reaction was taken up in CH2Cl2 (25 mL) and washed with a saturated aqueous ammonium chloride solution (25 mL). The aqueous solution was back-extracted with dichloromethane (2×10 mL), and combined organics were dried over MgSO4 and concentrated to a brown oil. Chromatography (3 cm×20 cm Silica gel, 3% MeOH/CH2Cl2) yielded azido-PEG8-yne (960 mg, 78% yield). IR (thin film/NaCl) 2874 (m), 2110 (m), 1160 (s), 1105 (s) cm−1; 1HNMR (400 MHz, CDCl3) δ 4.20 (d, J=2.4 Hz, 2H), 3.58 (m, 30H), 3.39 (t, J=5.1 Hz, 2H), 2.43 (t, J=2.4 Hz, 1H), 1.82 (s, 1H); 13CNMR (125 MHz, CDCl3) δ 79.82, 74.72, 70.75, 7022, 68.27, 58.62, 50.84; HRMS (ES+) calc'd for C19H35N3O8 (M+Na) m/z 456.231637. Found 456.23182. washed with a saturated aqueous ammonium chloride solution (25 mL) The aqueous solution was back-extracted with dichloromethane (2×10 mL) combined organics were dried over MgSO4 concentrated to a brown oil

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

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (azido-PEG8-ol) (1.1 g, 3.17 mmol, 1.0 equiv.) was dissolved in N,N′-dimethylformamide (6 mL), and sodium hydride (152 mg, 6.34 mmol, 2.0 equiv.) was added, followed by propargyl bromide (80% in PhMe, 683 μL 6.34 mmol, 2.0 equiv.). The reaction ran for 4 h at rt, at which time it was found complete by NMR aliquot. The reaction was taken up in CH2Cl2 (25 mL) and washed with a saturated aqueous ammonium chloride solution (25 mL). The aqueous solution was back-extracted with dichloromethane (2×10 mL), and combined organics were dried over MgSO4 and concentrated to a brown oil. Chromatography (3 cm×20 cm Silica gel, 3% MeOH/CH2Cl2) yielded azido-PEG8-yne (960 mg, 78% yield). IR (thin film/NaCl) 2874 (m), 2110 (m), 1160 (s), 1105 (s) cm−1; 1HNMR (400 MHz, CDCl3) δ 4.20 (d, J=2.4 Hz, 2H), 3.58 (m, 30H), 3.39 (t, J=5.1 Hz, 2H), 2.43 (t, J=2.4 Hz, 1H), 1.82 (s, 1H); 13CNMR (125 MHz, CDCl3) δ 79.82, 74.72, 70.75, 7022, 68.27, 58.62, 50.84; HRMS (ES+) calc'd for C19H35N3O8 (M+Na) m/z 456.231637. Found 456.23182. washed with a saturated aqueous ammonium chloride solution (25 mL) The aqueous solution was back-extracted with dichloromethane (2×10 mL) combined organics were dried over MgSO4 concentrated to a brown oil

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 23-Azido-3,6,9,12,15,18,21-heptaoxatricosan-1-ol (500 mg, 1.26 mmol) was dissolved in DCM (2 mL) and cooled to −10° C. DAST (482 μL, 3.78 mmol) was added in portions to the cooled solution and the resulting mixture was stirred at −10° C. for 30 minutes then allowed to warm to room temperature and stirred for additional 20 hours. The excess of DAST was quenched with methanol (5 mL) and the solvents were subsequently evaporated at the reduced pressure. The oily residue was dissolved in the water (3 mL) and the pH was adjusted to 5 using NaHCO3. The crude product was purified on semipreparative HPLC (System E) to yield 122 mg (24%) of 4 as a yellowish oil. 1H NMR (500 MHz, CDCl3): δ 3.39 (t, J=5.0 Hz, 2H), 3.65-3.68 (m, 26H), 3.75 (dt, J=4.2 Hz, 29.6 Hz, 2H), 4.56 (dt, J=4.0 Hz, 47.5 Hz, 2H); 13C NMR (125.7 MHz, CDCl3): δ 50.8, 70.1, 70.4, 70.5, 70.7-70.8, 70.9, 83.2 (d, J=169 Hz); 19F NMR (470.6 MHz, CDCl3): δ −225.9; MS ESI (m/z): [M+H]+ calcd. for C16H33FO7N3, 398.2. found 398.0. to warm to room temperature stirred for additional 20 hours The excess of DAST was quenched with methanol (5 mL) the solvents were subsequently evaporated at the reduced pressure The oily residue was dissolved in the water (3 mL) The crude product was purified on semipreparative HPLC (System E)