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CAS No. : | 39160-70-8 | MDL No. : | MFCD22200781 |
Formula : | C12H27NO6 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ICUIZKMGHRMMDZ-UHFFFAOYSA-N |
M.W : | 281.35 | Pubchem ID : | 20554065 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 5h; | 31 Preparation of Compound 21a Preparation of Compound 21a To a solution of compound 3b (9.0 g, 29.2 mmol) in MeOH (146 mL) was added Pd/C (10 wt. %, 3.0 g) and the reaction mixture was stirred at room temperature for 5 hours under hydrogen. Then the reaction mixture was filtered through a celite pad and washed with MeOH (100 mL). Concentration provided compound 21a (8.2 g, 100 %) as colorless oil, which was used without further purification. 1H-NMR (400MHz, CDC13) δ 3.80-3.60 (m, 24H), 3.01 (t, J= 4.8 Hz, 2H). |
100% | With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 5h; | 31 Preparation of Compound 21a To a solution of compound 3b (9.0 g, 29.2 mmol) in MeOH (146 mL) was added Pd/C (10 wt. %, 3.0 g) and the reaction mixture was stirred at room temperature for 5 hours under hydrogen. Then the reaction mixture was filtered through a celite pad and washed with MeOH (100 mL). Concentration provided compound 21a (8.2 g, 100 %) as colorless oil, which was used without further purification. 1H-NMR (400MHz, CDC13) δ 3.80-3.60 (m, 24H), 3.01 (t, J= 4.8 Hz, 2H). |
99% | With Adams’s catalyst; hydrogen In methanol for 2h; |
98% | Stage #1: 2-(2-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)ethoxy)ethanol With triphenylphosphine In tetrahydrofuran at 0 - 20℃; for 10h; Stage #2: With lithium hydroxide monohydrate In tetrahydrofuran | |
98% | Stage #1: 2-(2-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)ethoxy)ethanol With triphenylphosphine In tetrahydrofuran at 20℃; Stage #2: With lithium hydroxide monohydrate In tetrahydrofuran Further stages.; | |
98% | With lithium hydroxide monohydrate; triphenylphosphine In tetrahydrofuran | |
96% | With 10% palladium on activated carbon; hydrogen In ethanol; lithium hydroxide monohydrate for 48h; Autoclave; | |
95% | With palladium 10% on activated carbon; ammonia; hydrogen In methanol; lithium hydroxide monohydrate at 20℃; for 5h; | |
95% | With triphenylphosphine In tetrahydrofuran at 20℃; for 10h; | 4.S9 Synthesis of compound H Add compound G (197mg, 0.9mmol, 1.0eq.), triphenylphosphonium (260mg, 0.98mmol, 1.09eq.), 5mL anhydrous THF in a 50mL round bottom flask, under nitrogen protection React at room temperature for 10 hours, add 1 mL of water and continue to stir the reaction for 1 hour, stop the reaction, add 20 mL of water to dilute, wash with toluene 3 times, 50 mL each time, collect the aqueous phase, spin-dry the water, and vacuum dry to obtain compound H as a light-colored liquid , The yield is 95%. |
92% | With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; for 12h; | 3 Step 3-2-[2-[2-[2-[2-(2-Aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol To a solution of 2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol (10.0 g, 32.5 mmol) in EtOH (80.0 mL) was added Pd/C (4.00 g, 10 wt %). The reaction mixture was stirred under hydrogen atmosphere (15 psi pressure) at rt for 12 h. On completion, the mixture was filtered and concentrated in vacuo to give the title compound (8.50 g, 92% yield) as a light yellow oil. LC-MS (ESI)+ m/z 282.1. (M+H)+. |
86% | With triphenylphosphine In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; | |
79% | With formiate d'ammonium In methanol Ambient temperature; | |
78% | With palladium 10% on activated carbon; ammonia; hydrogen In methanol at 20℃; for 5h; | 1 To a stirred solution of 17-azido-3,6,9,12,15-pentaoxaheptadecan-l-ol 61 (1.4 g, 4.56 mmol) in dry methanol (20 mL) was added palladium on carbon (200 mg, 10% wt.) and 25% aqueous ammonia (5 mL). The resulting mixture was stirred at ambient temperature under FL balloon pressure for 5 h, and then filtered through a bed of Celite. The Celite bed was washed with methanol (2 x 25 mL), and the combined filtrates were concentrated under reduced pressure to afford 17-amino-3,6,9,12,15-pentaoxaheptadecan-l-ol, 62 (1 g, 78%) as a colorless liquid, which was used without further purification. |
78% | With palladium 10% on activated carbon; ammonia; hydrogen In methanol; lithium hydroxide monohydrate at 20℃; for 5h; Inert atmosphere; | 1 To a stirred solution of 17-azido-3,6,9,12,15-pentaoxaheptadecan-1-ol 61 (1.4 g, 4.56 mmol) in dry methanol (20 mL) was added palladium on carbon (200 mg, 10% wt.) and 25% aqueous ammonia (5 mL). The resulting mixture was stirred at ambient temperature under H2balloon pressure for 5 h, and then filtered through a bed of Celite. The Celite bed was washed with methanol (2 x 25 mL), and the combined filtrates were concentrated under reduced pressure to afford 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 78%) as a colorless liquid, which was used without further purification. |
78% | With ammonium hydroxide; palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 5h; | 1 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol (62) [0490] To a stirred solution of 17-azido-3,6,9,12,15-pentaoxaheptadecan-1-ol 61 (1.4 g, 4.56 mmol) in dry methanol (20 mL) was added palladium on carbon (200 mg, 10% wt.) and 25% aqueous ammonia (5 mL). The resulting mixture was stirred at ambient temperature under H2 balloon pressure for 5 h, and then filtered through a bed of Celite. The Celite bed was washed with methanol (2 x 25 mL), and the combined filtrates were concentrated under reduced pressure to afford 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 78%) as a colorless liquid, which was used without further purification. |
78% | With ammonium hydroxide; palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 5h; | 1 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol (62) [0490] To a stirred solution of 17-azido-3,6,9,12,15-pentaoxaheptadecan-1-ol 61 (1.4 g, 4.56 mmol) in dry methanol (20 mL) was added palladium on carbon (200 mg, 10% wt.) and 25% aqueous ammonia (5 mL). The resulting mixture was stirred at ambient temperature under H2 balloon pressure for 5 h, and then filtered through a bed of Celite. The Celite bed was washed with methanol (2 x 25 mL), and the combined filtrates were concentrated under reduced pressure to afford 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 78%) as a colorless liquid, which was used without further purification. |
78% | With palladium 10% on activated carbon; ammonia; hydrogen In methanol; lithium hydroxide monohydrate at 20℃; for 5h; Inert atmosphere; | 1 To a stirred solution of 17-azido-3,6,9,12,15-pentaoxaheptadecan-1-ol 61 (1.4 g, 4.56 mmol) in dry methanol (20 mL) was added palladium on carbon (200 mg, 10% wt.) and 25% aqueous ammonia (5 mL). The resulting mixture was stirred at ambient temperature under H2balloon pressure for 5 h, and then filtered through a bed of Celite. The Celite bed was washed with methanol (2 x 25 mL), and the combined filtrates were concentrated under reduced pressure to afford 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 78%) as a colorless liquid, which was used without further purification. |
56% | With lithium hydroxide monohydrate; triphenylphosphine In tetrahydrofuran for 5h; | |
Stage #1: 2-(2-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)ethoxy)ethanol With triphenylphosphine In pyridine at 20℃; for 2h; Stage #2: With ammonium hydroxide In pyridine at 20℃; for 2h; | ||
With palladium on activated charcoal; hydrogen In ethanol for 1h; | 28 tert-Butyl 3,6,9,12,15,18-Hexaoxahenicos-20-yn-l-ylcarbamate (58). A mixture of azide (2.98 g, 9.7 mmol) and Pd/C (100 mg) in EtOH (50 mL) was stirred under H2 (60 psi) for 1 h. The mixture was filtered through Celite and washed with EtOH (3 x 20 mL) and the solvent was evaporated. The crude residue was dissolved in DCM (50 mL) and di- ie/t-butyl dicarbonate (2.56 g, 11.7 mmol) in DCM (20 mL) was added dropwise and the solution was stirred at 20 °C for 16 h. The solvent was evaporated and residue was purified by column chromatography, eluting with 10% MeOH/EtOAc, to give tert- butyl 17-hydroxy-3,6,9,12,15-pentaoxaheptadec-l-ylcarbamate (2.97 g, 80%) as a colourless oil: 1H NMR (CDC13) δ 5.17 (br s, 1 H, NHC02), 3.70-3.74 (m, 2 H, CH20), 3.60-3.68 (m, 18 H, 9 x CH20), 3.54 (br t, J = 5.1 Hz, 2 H, CH20), 3.31 (br q, J = 5.1 Hz, 2 H, CH2N), 2.81 (br s, 1 H, OH), 1.44 [s, 9 H, C(CH3)3]; MS m/z 382.5 (MH+, 100%). | |
With palladium on activated charcoal; hydrogen In ethanol for 1h; | 12 tert-Butyl 17-hydroxy-3,6,9,12,15-pentaoxaheptadec-1-ylcarbamate (23) A mixture of azide 22 (2.98 g, 9.7 mmol) and Pd/C (100 mg) in EtOH (50 mL) was stirred under H2 (60 psi) for 1 h. The mixture was filtered through diatomaceous earth and washed with EtOH (3 * 20 mL) and the solvent was evaporated. The crude residue was dissolved in DCM (50 mL) and di-tert-butyl dicarbonate (2.56 g, 11.7 mmol) in DCM (20 mL) was added dropwise and the solution was stirred at 20 °C for 16 h. The solvent was evaporated and residue was purified by column chromatography, eluting with 10% MeOH/EtOAc, to give carbamate 23 (2.97 g, 80%) as a colourless oil | |
Stage #1: 2-(2-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)ethoxy)ethanol With triphenylphosphine In tetrahydrofuran Stage #2: With lithium hydroxide monohydrate In tetrahydrofuran | ||
With palladium on activated charcoal | ||
52 g | With palladium on activated charcoal; hydrogen In methanol | 16 To a 1L hydrogenation reactor were added BP103g02 70g, methanol 500 mL, palladium on carbon 8.0g, stirred, with nitrogen replaced by introducing hydrogen to react for 3-4h. After the completion of the reaction under the monitor of TLC, the reaction liquid was filtered, and the filtrate was concentrated to give 52g BP103g03 as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With hydrogen |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.53 g | With N-ethyl-N,N-diisopropylamine In water; N,N-dimethyl-formamide at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide at 0℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.4 g | With hydrazine In methanol for 3h; Heating; | |
With hydrazine In methanol for 2h; Reflux; | Synthesis methacrylatederivative bearing PEG2000 as hydrophilic spacer (7) General procedure: To a mixture of PEG2000 (21.02 g, 10.5 mmol), phtalimide (1.7 g, 11.6 mmol), triphenylphosphine (3.31 g, 12.6 mmol) and THF(150 mL), diethyl azodicarboxylate (40 wt.% in toluene) was added dropwise over 10 min at ambient temperature and was stirred overnight. The reaction mixture was poured into a mixture of water and CHCl3, and the separated organic layer washed with brine, and was dried over anhydrous magnesium sulfate (MgSO4). After filtration, the filtrate was evaporated in vacuo to give crude compound A (ca.23 g), was used in the next step without further purification. A mixture of compound A (23 g), hydrazine hydrate (1.05 mL, 21.6 mmol), and MeOH (100 mL) was stirred at reflux for 2 h. After being cooled to ambient temperature, the resulting precipitates were filtered off by filtration. The filtrate was evaporated in vacuo and purified by column chromatography on silica gel (for wash; 10% MeOH in CHCl3, forelution 20% MeOH in CHCl3). Fractions containing the desired compound were collected (not a single spot, detected by the ninhydrin test and iodine) and evaporated in vacuo to give compound B (4.12 g, 19% for 2 steps |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine In methanol at 20℃; for 18h; | 1 To a stirred solution of 17-amino-3,6,9,12,15-pentaoxaheptadecan-l-ol, 62 (1 g, 3.55 mmol) in dry methanol (25 mL) was added triethylamine (0.6 mL, 4.26 mmol) and Boc anhydride (853 mg, 3.91 mmol). The resulting solution was stirred at ambient temperature for 18 h and then concentrated under reduced pressure to afford ter/-butyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate, 63 (1.4 g, 99%) as a colorless liquid, which was used without further purification. |
99% | With triethylamine In methanol at 20℃; for 18h; Inert atmosphere; | 1 To a stirred solution of 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 3.55 mmol) in dry methanol (25 mL) was added triethylamine (0.6 mL, 4.26 mmol) and Boc anhydride (853 mg, 3.91 mmol). The resulting solution was stirred at ambient temperature for 18 h and then concentrated under reduced pressure to afford tert-butyl (17-hydroxy-3,6,9,12,15- pentaoxaheptadecyl)carbamate, 63 (1.4 g, 99%) as a colorless liquid, which was used without further purification. |
99% | With triethylamine In methanol at 20℃; for 18h; | 1 tert-butyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate (63) [0491] To a stirred solution of 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 3.55 mmol) in dry methanol (25 mL) was added triethylamine (0.6 mL, 4.26 mmol) and Boc anhydride (853 mg, 3.91 mmol). The resulting solution was stirred at ambient temperature for 18 h and then concentrated under reduced pressure to afford tert-butyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate, 63 (1.4 g, 99%) as a colorless liquid, which was used without further purification. |
99% | With triethylamine In methanol at 20℃; for 18h; | 1 tert-butyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate (63) [0491] To a stirred solution of 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 3.55 mmol) in dry methanol (25 mL) was added triethylamine (0.6 mL, 4.26 mmol) and Boc anhydride (853 mg, 3.91 mmol). The resulting solution was stirred at ambient temperature for 18 h and then concentrated under reduced pressure to afford tert-butyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate, 63 (1.4 g, 99%) as a colorless liquid, which was used without further purification. |
99% | With triethylamine In methanol at 20℃; for 18h; Inert atmosphere; | 1 To a stirred solution of 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol, 62 (1 g, 3.55 mmol) in dry methanol (25 mL) was added triethylamine (0.6 mL, 4.26 mmol) and Boc anhydride (853 mg, 3.91 mmol). The resulting solution was stirred at ambient temperature for 18 h and then concentrated under reduced pressure to afford tert-butyl (17-hydroxy-3,6,9,12,15- pentaoxaheptadecyl)carbamate, 63 (1.4 g, 99%) as a colorless liquid, which was used without further purification. |
98% | In ethyl acetate at 60℃; for 1.5h; | Synthesis ofN-(tert-butoxycarbonyl)-17-amino-3,6,9,12,15-pentaoxaheptadecane-1-ol (14) To a solution of linker 13 (0.65 g, 2.3 mmol) in ethyl acetate (15 mL) di-tert-butyl dicarbonate (0.56 g, 2.6 mmol) was added. The reaction mixture was stirred at 60 °C for 90 min. The solution was cooled to rt and diluted with ethyl acetate (30 mL). The organic layer was washed two times with brine (20 mL each), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was chromatographed on a silica gel column with DCM-methanol (9:1) to give compound 14 (797 mg, 98%) as a clear syrup.1H NMR (300 MHz, CDCl3) δ (ppm) 3.74-3.52 (m, 22 H, CH2CH2-O), 3.31 (br, 2 H, CH2-NH), 2.76 (br, 1 H, OH), 1.44 (s, 9 H, C(CH3)3); 13C NMR (300 MHz, CDCl3) δ (ppm) 155.98 (Boc-CO), 79.33 (C(CH3)3), 76.58 (CH2-O), 72.48 (CH2-O), 70.54 (CH2-O), 70.30 (CH2-O), 70.19 (CH2-O), 61.67 (CH2-OH), 40.34 (CH2-NH), 28,39 (C(CH3)3); MALDI-TOF (m/z) calcd for C17H35NO8 = 381.24 found 404.19 (M+Na+) |
97% | With triethylamine In methanol at 20℃; | |
89% | In dichloromethane | |
69.2% | With triethylamine In dichloromethane at 10 - 20℃; for 16h; Inert atmosphere; | 1 General procedure for preparation of amine 13 - To a solution of compound 13a (650 mg, 2.31 mmol) and TEA (468 mg, 4.63 mmol) in DCM (6.50 mL ) was added dropwise (Boc)20 (706 mg, 3.23 mmol) at 10-20 °C under N2 atmosphere and kept stirred at 10-20 °C for 16 h under N2 atmosphere. TLC (DCM/Methanol = 10/1 ) showed compound 13a (Rf = 0.00) was disappeared and new spot (Rf = 0.52) was found. The reaction mixture was concentrated under reduce pressure. The residue was purified by flash silica gel chromatography (ISCO; X g SepaFlash Silica Flash Column, Eluent of 0~2% Methanol/DCM). Amine 13 (610 mg, 1.60 mmol, 69.2% yield) was obtained as a colorless oil which was confirmed by 1H NMR. 1H NMR:, 400 MHz, CDCI3 δ 5.22 (s, 1 H), 3.59-3.77 (m, 20 H), 3.55 (t, J= 5.2 Hz, 2H), 3.32 (d, J= 5.2 Hz, 2H), 2.87-3.07 (m, 1 H), 1.45 (s, 9H) |
59% | Stage #1: di-<i>tert</i>-butyl dicarbonate; 2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol In 1,4-dioxane at 0℃; for 3h; Stage #2: With triethylamine at 20℃; | |
28 g | With potassium carbonate In methanol at 20℃; for 15h; | |
2.97 g | In dichloromethane at 20℃; for 16h; | 28 tert-Butyl 3,6,9,12,15,18-Hexaoxahenicos-20-yn-l-ylcarbamate (58). A mixture of azide (2.98 g, 9.7 mmol) and Pd/C (100 mg) in EtOH (50 mL) was stirred under H2 (60 psi) for 1 h. The mixture was filtered through Celite and washed with EtOH (3 x 20 mL) and the solvent was evaporated. The crude residue was dissolved in DCM (50 mL) and di- ie/t-butyl dicarbonate (2.56 g, 11.7 mmol) in DCM (20 mL) was added dropwise and the solution was stirred at 20 °C for 16 h. The solvent was evaporated and residue was purified by column chromatography, eluting with 10% MeOH/EtOAc, to give tert- butyl 17-hydroxy-3,6,9,12,15-pentaoxaheptadec-l-ylcarbamate (2.97 g, 80%) as a colourless oil: 1H NMR (CDC13) δ 5.17 (br s, 1 H, NHC02), 3.70-3.74 (m, 2 H, CH20), 3.60-3.68 (m, 18 H, 9 x CH20), 3.54 (br t, J = 5.1 Hz, 2 H, CH20), 3.31 (br q, J = 5.1 Hz, 2 H, CH2N), 2.81 (br s, 1 H, OH), 1.44 [s, 9 H, C(CH3)3]; MS m/z 382.5 (MH+, 100%). |
2.97 g | In dichloromethane at 20℃; for 16h; | 12 tert-Butyl 17-hydroxy-3,6,9,12,15-pentaoxaheptadec-1-ylcarbamate (23) A mixture of azide 22 (2.98 g, 9.7 mmol) and Pd/C (100 mg) in EtOH (50 mL) was stirred under H2 (60 psi) for 1 h. The mixture was filtered through diatomaceous earth and washed with EtOH (3 * 20 mL) and the solvent was evaporated. The crude residue was dissolved in DCM (50 mL) and di-tert-butyl dicarbonate (2.56 g, 11.7 mmol) in DCM (20 mL) was added dropwise and the solution was stirred at 20 °C for 16 h. The solvent was evaporated and residue was purified by column chromatography, eluting with 10% MeOH/EtOAc, to give carbamate 23 (2.97 g, 80%) as a colourless oil: 1H NMR (CDCl3) δ 5.17 (br s, 1H, NHCO2), 3.70-3.74 (m, 2H, CH2O), 3.60-3.68 (m, 18 H, 9 * CH2O), 3.54 (br t, J = 5.1 Hz, 2H, CH2O), 3.31 (br q, J = 5.1 Hz, 2H, CH2N), 2.81 (br s, 1H, OH), 1.44 [s, 9 H, C(CH3)3]; MS m/z 382.5 (MH+, 100%). |
With triethylamine In dichloromethane at 20℃; | Synthesis methacrylatederivative bearing PEG2000 as hydrophilic spacer (7) General procedure: To a mixture of PEG2000 (21.02 g, 10.5 mmol), phtalimide (1.7 g, 11.6 mmol), triphenylphosphine (3.31 g, 12.6 mmol) and THF(150 mL), diethyl azodicarboxylate (40 wt.% in toluene) was added dropwise over10 min at ambient temperature andwas stirred overnight. The reaction mixture was poured into a mixture of water and CHCl3, and the separated organic layer washed with brine, andwas dried over anhydrous magnesium sulfate (MgSO4). After filtration, the filtrate was evaporated invacuo to give crude compound A (ca.23 g), was used in the next step without further purification. A mixture of compound A (23 g), hydrazine hydrate (1.05 mL,21.6 mmol), and MeOH (100 mL) was stirred atreflux for 2 h. After being cooled to ambient temperature, the resulting precipitates were filtered off by filtration. The filtrate was evaporated in vacuo and purified by column chromatography on silica gel (for wash; 10% MeOH in CHCl3,for elution 20% MeOH in CHCl3). Fractions containing the desired compound were collected (not a single spot, detected by the ninhydrin test andiodine) and evaporated in vacuo togive compound B (4.12 g, 19% for 2steps, average MW=1999). ESI-HRMS calcd. for H2N-(C2H4O)n-OH(n=40, ([M+H+Na2]3+) 623.0290;found m/z 623.0293,H2N-(C2H4O)n-OH (n=41, ([M+H+Na2]3+) 637.7044;found m/z 637.7058,H2N-(C2H4O)n-OH (n=42, ([M+H+Na2]3+) 652.7143;found m/z 652.7155,H2N-(C2H4O)n-OH (n=43, ([M+H+Na2]3+) 667.0552;found m/z 667.0564,H2N-(C2H4O)n-OH (n=44, ([M+H+Na2]3+) 681.7306;found m/z 681.7312,H2N-(C2H4O)n-OH (n=45, ([M+H+Na2]3+) 696.7405;found m/z 696.7389,H2N-(C2H4O)n-OH (n=46, ([M+H+Na2]3+) 711.4159;found m/z 711.4156,H2N-(C2H4O)n-OH (n=47, ([M+H+Na2]3+) 726.0913;found m/z 726.0892,H2N-(C2H4O)n-OH (n=48, ([M+H+Na2]3+) 740.7667;found m/z 740.7644. A mixture of compound B (4.12 g, 2.06 mmol), di-tert butyl dicarbonate (720 mg, 3.3mmol), triethyl amine (250 mg, 2.47 mmol), and CH2Cl2(100 mL) was stirred at ambient temperature overnight. The reaction mixture was poured into a mixture of saturated aqueous solution of NaHCO3and CHCl3, and the separated organic layer washed with water, brine,and was dried over anhydrous magnesium sulfate (MgSO4). After filtration, the filtrate was evaporated in vacuo to give crude compound C (ca. 4.5 g, average MW=2099), was used in the next step without further purification. | |
9 g | With triethylamine In methanol for 1h; Reflux; | 16 To a 250mL three-necked flask were added compound BP103g03 10.0g (1. 0eq), (Boc)2O 15.5g (2.0 eq), a mixed solution of methanol:triethylamine (9:1) 200ml, stirred and warmed to reflux, and reacted for 1h. After the completion of the reaction under the monitor of TLC, methanol triethylamine was evaporated off, and dissolved with water. Dichloromethane was extracted for 3 times. The organic layers were combined and washed once with water, dried over anhydrous sodium sulfate, and concentrated to give 9.0g BP103g04 as an oil. |
In tetrahydrofuran at 0 - 20℃; for 5h; | 172 To a stirred solution of 2-[2-[2-[2-[2-(2- aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol (500.0 mg, 1.78 mmol) in THF (10 mL) at 0°C, di-tert-butyl dicarbonate (465.43 mg, 2.13 mmol) was added portionwise. The mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic phases were washed with brine, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography (KP-Sil silica gel, SNAP 25) eluting with EtOAc to give tert-butyl N-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate (680 mg, 1.783 mmol, 100.31% yield) as a colorless oil.1H NMR (400 MHz, DMSO-d6) δ 1.38 (s, 9H), 3.06 (q, J = 6.03 Hz, 2H), 3.35 - 3.44 (m, 4H), 3.51 (dd, J = 5.82, 0.98 Hz, 18H), 4.56 (br. s, 1H), 6.74 (s, 1H). | |
In tetrahydrofuran at 0 - 20℃; for 5h; | 172 To a stirred solution of 2-[2-[2-[2-[2-(2- aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol (500.0 mg, 1.78 mmol) in THF (10 mL) at 0°C, di-tert-butyl dicarbonate (465.43 mg, 2.13 mmol) was added portionwise. The mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic phases were washed with brine, dried over sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography (KP-Sil silica gel, SNAP 25) eluting with EtOAc to give tert-butyl N-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate (680 mg, 1.783 mmol, 100.31% yield) as a colorless oil.1H NMR (400 MHz, DMSO-d6) δ 1.38 (s, 9H), 3.06 (q, J = 6.03 Hz, 2H), 3.35 - 3.44 (m, 4H), 3.51 (dd, J = 5.82, 0.98 Hz, 18H), 4.56 (br. s, 1H), 6.74 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In N,N-dimethyl-formamide at 110℃; for 8h; Inert atmosphere; | |
42% | In isopropyl alcohol for 15h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 63 percent / Ag2O / CH2Cl2 / 48 h 2.1: 92 percent / NaN3 / dimethylformamide / 2.5 h / 110 °C 3.1: triphenyl phosphine / tetrahydrofuran / 10 h / 0 - 20 °C 3.2: 98 percent / water / tetrahydrofuran | ||
Multi-step reaction with 2 steps 1: diisopropyl azodicarboxylate; triphenylphosphine / tetrahydrofuran / 15 h / 20 °C 2: 21.4 g / N2H4 / methanol / 3 h / Heating | ||
Multi-step reaction with 3 steps 1.1: 60 percent / Ag2O / CH2Cl2 / 48 h 2.1: 90 percent / sodium azide / dimethylformamide / 110 °C 3.1: Ph3P / tetrahydrofuran / 20 °C 3.2: 98 percent / H2O / tetrahydrofuran |
Multi-step reaction with 3 steps 1: 72 percent / triethylamine; 4-dimethylaminopyridine / CH2Cl2 / 4 h / cooling 2: 81 percent / sodium azide / acetonitrile / 32 h / Heating 3: 56 percent / triphenylphosphine; water / tetrahydrofuran / 5 h | ||
Multi-step reaction with 4 steps 1: 72 percent / 50percent NaOH / H2O / 24 h / Heating 2: 93 percent / PPh3, CCl4 / 24 h / Heating 3: 98 percent / NaN3 4: 91 percent / H2 / Pd | ||
Multi-step reaction with 2 steps 1.1: pyridine; p-toluenesulfonyl chloride / tetrahydrofuran / 2.5 h / Inert atmosphere 1.2: Reflux 2.1: triphenylphosphine / tetrahydrofuran / 12 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: silver(I) oxide / dichloromethane / 72 h / 20 °C 2: Caswell No. 744A / N,N-dimethyl-formamide / 2 h / 110 °C 3: palladium on activated charcoal; hydrogen / ethanol / 1 h / 3102.97 Torr | ||
Multi-step reaction with 3 steps 1: silver(I) oxide / dichloromethane / 72 h / 20 °C 2: Caswell No. 744A / N,N-dimethyl-formamide / 2 h / 110 °C 3: hydrogen; palladium on activated charcoal / ethanol / 1 h / 3102.97 Torr | ||
Multi-step reaction with 3 steps 1: silver(I) oxide; potassium iodide / dichloromethane / 1.5 h / 0 °C 2: Caswell No. 744A / N,N-dimethyl-formamide / 16 h / 50 °C 3: triphenylphosphine / tetrahydrofuran | ||
Multi-step reaction with 2 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran; toluene / 20 °C 2: hydrazine / methanol / 2 h / Reflux | ||
Multi-step reaction with 3 steps 1: potassium iodide; silver(I) oxide / dichloromethane / 3 h / 0 °C 2: Caswell No. 744A / N,N-dimethyl-formamide / 16 h / 50 °C 3: palladium 10% on activated carbon; hydrogen; ammonia / methanol; water monomer / 5 h / 20 °C | ||
Multi-step reaction with 3 steps 1: potassium iodide; silver(I) oxide / dichloromethane / 0.25 h / -30 - 0 °C 2: Caswell No. 744A / N,N-dimethyl-formamide / 15 h / 100 °C 3: palladium 10% on activated carbon; hydrogen / methanol / 5 h / 20 °C | ||
Multi-step reaction with 3 steps 1.1: potassium iodide; silver(I) oxide / dichloromethane / 0.25 h / Sonication 1.2: 0.25 h / -30 - 0 °C 2.1: Caswell No. 744A / N,N-dimethyl-formamide / 15 h / 100 °C 3.1: palladium 10% on activated carbon; hydrogen / methanol / 5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: p-toluenesulfonyl chloride; triethylamine / chloroform 2: palladium on activated charcoal | ||
Multi-step reaction with 3 steps 1: pyridine / 0 - 20 °C / Inert atmosphere 2: Caswell No. 744A / dimethyl sulfoxide / 3 h / 50 °C 3: palladium on activated charcoal; hydrogen / methanol | ||
Multi-step reaction with 3 steps 1: silver(I) oxide; potassium iodide / 24 h / 20 °C / Inert atmosphere 2: Caswell No. 744A / N,N-dimethyl-formamide / 12 h / 80 °C 3: hydrogen; palladium 10% on activated carbon / ethanol / 12 h / 20 °C / 775.74 Torr | ||
Multi-step reaction with 3 steps 1: potassium iodide; silver(I) oxide / dichloromethane / 24 h / 20 °C 2: Caswell No. 744A / acetonitrile / 22 h / Inert atmosphere; Reflux 3: triphenylphosphine / tetrahydrofuran / 10 h / 20 °C | ||
Multi-step reaction with 3 steps 1: silver(I) oxide; potassium iodide / dichloromethane / 2 h / 20 °C / Inert atmosphere 2: Caswell No. 744A / N,N-dimethyl-formamide / 8 h / 50 °C / Inert atmosphere 3: palladium 10% on activated carbon; hydrogen; ammonia / methanol / 5 h / 20 °C | ||
Multi-step reaction with 3 steps 1: silver(I) oxide; potassium iodide / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2: Caswell No. 744A / N,N-dimethyl-formamide / 8 h / 20 - 50 °C / Inert atmosphere 3: palladium 10% on activated carbon; hydrogen; ammonium hydroxide / methanol / 5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 80 percent / HOBt; EDCl; Et3N / CH2Cl2 / 20 h / 0 - 20 °C 2.1: 1,1,1,3,3,3-hexamethyldisilazane / Heating 2.2: 43 percent / DMAP; EDC / CH2Cl2 / 15 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 92 percent / NaN3 / dimethylformamide / 2.5 h / 110 °C 2.1: triphenyl phosphine / tetrahydrofuran / 10 h / 0 - 20 °C 2.2: 98 percent / water / tetrahydrofuran | ||
Multi-step reaction with 2 steps 1.1: 90 percent / sodium azide / dimethylformamide / 110 °C 2.1: Ph3P / tetrahydrofuran / 20 °C 2.2: 98 percent / H2O / tetrahydrofuran | ||
Multi-step reaction with 2 steps 1: sodium azide / N,N-dimethyl-formamide / 2 h / 110 °C 2: palladium on activated charcoal; hydrogen / ethanol / 1 h / 3102.97 Torr |
Multi-step reaction with 2 steps 1: sodium azide / N,N-dimethyl-formamide / 2 h / 110 °C 2: hydrogen; palladium on activated charcoal / ethanol / 1 h / 3102.97 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 28 g / potassium carbonate / methanol / 15 h / 20 °C 2: 51 percent / N,N,N',N'-tetramethyl-1,3-diaminopropane / acetonitrile / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 75 percent / N-hydroxybenzotriazole; N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide / CH2Cl2 / 12 h / 20 °C 2: 95 percent / AcCl / methanol / 5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 76 percent / N-hydroxybenzotriazole; N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide / CH2Cl2 / 12 h / 20 °C 2: 70 percent / AcCl / methanol / 5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 59 percent / N-hydroxybenzotriazole; N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide / CH2Cl2 / 12 h / 20 °C 2: 80 percent / AcCl / methanol / 5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 85 percent / N-hydroxybenzotriazole; N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide / CH2Cl2 / 12 h / 20 °C 2: 82 percent / AcCl / methanol / 5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 81 percent / sodium azide / acetonitrile / 32 h / Heating 2: 56 percent / triphenylphosphine; water / tetrahydrofuran / 5 h | ||
Multi-step reaction with 2 steps 1: Caswell No. 744A / N,N-dimethyl-formamide / 16 h / 50 °C 2: palladium 10% on activated carbon; hydrogen; ammonia / methanol; water monomer / 5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: Caswell No. 744A / N,N-dimethyl-formamide / 15 h / 100 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 5 h / 20 °C |
Multi-step reaction with 2 steps 1: Caswell No. 744A / dimethyl sulfoxide / 3 h / 50 °C 2: palladium on activated charcoal; hydrogen / methanol | ||
Multi-step reaction with 2 steps 1: Caswell No. 744A / N,N-dimethyl-formamide / 12 h / 80 °C 2: hydrogen; palladium 10% on activated carbon / ethanol / 12 h / 20 °C / 775.74 Torr | ||
Multi-step reaction with 2 steps 1: Caswell No. 744A / acetonitrile / 22 h / Inert atmosphere; Reflux 2: triphenylphosphine / tetrahydrofuran / 10 h / 20 °C | ||
Multi-step reaction with 2 steps 1: Caswell No. 744A / N,N-dimethyl-formamide / 8 h / 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen; ammonia / methanol / 5 h / 20 °C | ||
Multi-step reaction with 2 steps 1: Caswell No. 744A / N,N-dimethyl-formamide / 8 h / 20 - 50 °C / Inert atmosphere 2: palladium 10% on activated carbon; hydrogen; ammonium hydroxide / methanol / 5 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: NaH / dimethylformamide / 2 h / 50 °C 2.1: 1.34 g / AcOH / tetrahydrofuran; H2O / 4 h / 20 °C 3.1: PPh3 / pyridine / 2 h / 20 °C 3.2: conc. NH4OH / pyridine / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 71 percent / DMAP / pyridine / 16 h / 20 °C 2.1: NaH / dimethylformamide / 2 h / 50 °C 3.1: 1.34 g / AcOH / tetrahydrofuran; H2O / 4 h / 20 °C 4.1: PPh3 / pyridine / 2 h / 20 °C 4.2: conc. NH4OH / pyridine / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 1.53 g / iPr2NEt / dimethylformamide; H2O / 0.5 h / 20 °C 2: 75 percent / TMSOTf; molecular sieves 4 Angstroem / CH2Cl2 / 0.17 h / -20 °C 3: 88 percent / t-BuOK / methanol / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.53 g / iPr2NEt / dimethylformamide; H2O / 0.5 h / 20 °C 2: 75 percent / TMSOTf; molecular sieves 4 Angstroem / CH2Cl2 / 0.17 h / -20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 1.53 g / iPr2NEt / dimethylformamide; H2O / 0.5 h / 20 °C 2: 56 percent / TMSOTf; molecular sieves 4 Angstroem / CH2Cl2 / 0.5 h / -20 °C 3: 95 percent / t-BuOK / methanol / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 1.53 g / iPr2NEt / dimethylformamide; H2O / 0.5 h / 20 °C 2: 56 percent / TMSOTf; molecular sieves 4 Angstroem / CH2Cl2 / 0.5 h / -20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 1.34 g / AcOH / tetrahydrofuran; H2O / 4 h / 20 °C 2.1: PPh3 / pyridine / 2 h / 20 °C 2.2: conc. NH4OH / pyridine / 2 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 93 percent / PPh3, CCl4 / 24 h / Heating 2: 98 percent / NaN3 3: 91 percent / H2 / Pd |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 98 percent / NaN3 2: 91 percent / H2 / Pd |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; potassium <i>tert</i>-butylate In tetrahydrofuran; sodium chloride | Synthesis for Step 1 (1) Synthesis of Aminohexaethylene Glycol t-butylcarbazate Spacer (4) Synthesis Route: Synthesis for Step 1 (1) 51.05 g (175.4 mmol) hexaethylene glycol is dissolved in 90 ml absolute THF and mixed with 211 mg (1.8 mmol) potassium tert-butylate. 9.2 ml acrylic acid tert.-butyl ester, dissolved in 15 ml dry THF, is added dropwise with stirring at room temperature over a period of 30 min. The preparation is stirred for 16 h at room temperature. The reaction mixture is neutralized, with stirring, with 2 ml of 1 N HCl. The solvent is removed under vacuum, and the oily residue is taken up in 50 ml of saturated NaCl solution and extracted three times with 50 ml dichloromethane. The organic phases are combined, dried over Na2SO4, filtered and the solvent is removed under vacuum. The oily residue is purified by column chromatography (silica gel; ethyl acetate:methanol=4:1). After drying under high vacuum, 20.25 g is obtained as a light yellowish oil. Rf=0.63 (ethyl acetate: methanol=4:1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | In acetonitrile for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | Stage #1: 4-methoxy-3,5-bis(tetradecyloxy)benzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: 3,6,9,12,15,18-hexaoxa-1-octadecyl amine In dichloromethane at 20℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: 3,4,5-tris(tetradecyloxy)benzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: 3,6,9,12,15,18-hexaoxa-1-octadecyl amine In dichloromethane at 20℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1.1: 1,4-dioxane / 3 h / 0 °C 1.2: 20 °C 2.1: triethylamine; p-toluenesulfonyl chloride / tetrahydrofuran / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C 4.1: potassium hydroxide / ethanol; water / Reflux 5.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Darkness 6.1: triethylamine / dichloromethane / 5 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: 1,4-dioxane / 3 h / 0 °C 1.2: 20 °C 2.1: triethylamine; 4-methylbenzene-1-sulfonyl chloride / tetrahydrofuran / 20 °C | ||
Multi-step reaction with 2 steps 1: Sodium hydrogenocarbonate / tetrahydrofuran / 3 h / 20 °C 2: triethylamine / dichloromethane / 0 - 20 °C | ||
Multi-step reaction with 2 steps 1: triethylamine / methanol / 18 h / 20 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 0 - 20 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1: triethylamine / methanol / 18 h / 20 °C / Inert atmosphere 2: sodium hydroxide / tetrahydrofuran / 18 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: triethylamine / methanol / 18 h / 20 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 0 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: 1,4-dioxane / 3 h / 0 °C 1.2: 20 °C 2.1: triethylamine; p-toluenesulfonyl chloride / tetrahydrofuran / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: 1,4-dioxane / 3 h / 0 °C 1.2: 20 °C 2.1: triethylamine; p-toluenesulfonyl chloride / tetrahydrofuran / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C 4.1: potassium hydroxide / ethanol; water / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: 1,4-dioxane / 3 h / 0 °C 1.2: 20 °C 2.1: triethylamine; p-toluenesulfonyl chloride / tetrahydrofuran / 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 4 h / 100 °C 4.1: potassium hydroxide / ethanol; water / Reflux 5.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 20 °C / Darkness |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: dichloromethane / 16 h / 20 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 16 h / 20 °C | ||
Multi-step reaction with 2 steps 1.1: dichloromethane / 16 h / 20 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 16 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: dichloromethane / 16 h / 20 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 16 h / 20 °C 3.1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / N,N-dimethyl-formamide / 16 h / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: dichloromethane / 16 h / 20 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 16 h / 20 °C 3.1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / N,N-dimethyl-formamide / 16 h / 70 °C 4.1: hydrogen; palladium 10% on activated carbon / methanol / 2.5 h / 20 °C / 3102.97 Torr |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: dichloromethane / 16 h / 20 °C 2.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 2.2: 16 h / 20 °C 3.1: bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine / N,N-dimethyl-formamide / 16 h / 70 °C 4.1: hydrogen; palladium 10% on activated carbon / methanol / 2.5 h / 20 °C / 3102.97 Torr 5.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
29% | With sodium hydrogencarbonate In water at 0 - 20℃; for 0.833333h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water / 0.83 h / 0 - 20 °C / Inert atmosphere 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 4 h / 0 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dichloromethane / 12 h / Inert atmosphere; Reflux 2: triethylamine / dichloromethane / 12 h / 0 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dichloromethane / 12 h / Inert atmosphere; Reflux 2: dmap / acetonitrile / 12 h / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In dichloromethane for 12h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In N,N-dimethyl-formamide for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: triethylamine / methanol / 20 °C 2: sodium hydroxide / water; tetrahydrofuran / 16 h / 20 °C 3: sodium azide / N,N-dimethyl-formamide / 16 h / 50 °C | ||
Multi-step reaction with 4 steps 1: sodium hydrogencarbonate / water; acetonitrile / 12 h / 20 °C 2: 10 wt% Pd(OH)2 on carbon / ethyl acetate / 12 h / 20 °C 3: triethylamine / dichloromethane / 1 h / 0 °C 4: sodium azide / N,N-dimethyl-formamide / 16 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90 mg | In N,N-dimethyl-formamide | 14.1 Synthesis of Compound 94n N-Boc-L-phenylalanine (80 mg, 0.28 mmol) was dissolved in DMF (3 mL), and the solution was cooled to 0°C, to which 17-amino-3,6,9,12,15-pentaoxaheptanol (68 mg, 0.26 mmol), HOBt (35 mg, 0.26 mmol) and EDCI (50 mg, 0.26 mmol) were sequentially added. The reaction mixture was warmed to rt and stirred for 24 h. The mixture was concentrated to remove the solvent, and the residue was dissolved in EtOAc. The organic phase was washed sequentially with water, 1 N hydrochloric acid, 1 N sodium hydroxide solution, and brine, dried, and concentrated. The residue was purified by silica gel chromatography (DCM/MeOH 30:1) to give compound 94n (90 mg). LC-MS (Method 1): R = 1.40 mm; m/z (ESj = 529.3 (M+H)t ‘H NMR (500 MHz, CDC13) 5 7.30-7.20 (m, 5 H), 4.36 (br s, 1 H), 3.75-3.40 (m, 21 H), 3.25-2.90 (m, 6 H), 1.39 (s, 9 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux | ||
Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Reflux | ||
Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere; Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C 2.2: -78 - 20 °C | ||
Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / -78 °C 2.2: -78 - 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 4 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere |
Multi-step reaction with 4 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere; Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 4 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere |
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere; Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 5.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C | ||
Multi-step reaction with 6 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 6.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C | ||
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 5.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C |
Multi-step reaction with 6 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere; Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 6.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 4 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere |
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere; Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 5.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C | ||
Multi-step reaction with 6 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 6.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C | ||
Multi-step reaction with 5 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 1.5 h / -78 °C 2.2: -78 - 20 °C 3.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 4.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 5.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C |
Multi-step reaction with 6 steps 1.1: triethylamine / tetrahydrofuran / 0 °C / Inert atmosphere 2.1: Methanesulfonic anhydride; 4-methyl-morpholine / tetrahydrofuran / 5 h / 0 °C / Inert atmosphere 2.2: 16 h / Inert atmosphere; Reflux 3.1: triphenylphosphine / tetrahydrofuran / 2 h / 20 °C / Inert atmosphere 3.2: 3 h / Inert atmosphere; Reflux 4.1: sodium cyanoborohydride / methanol / 3 h / 20 °C / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate / N,N-dimethyl-formamide / 6 h / 20 °C / Inert atmosphere 6.1: palladium 10% on activated carbon; hydrogen / methanol / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium hydrogencarbonate In water; acetonitrile at 20℃; for 12h; | 4 Step 4-Benzyl N-[2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethyl]carbamate To a solution of 2-[2-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol (4.00 g, 14.2 mmol) in ACN (40.0 mL) and H2O (40.0 mL) was added NaHCO3 (3.58 g, 42.6 mmol) and CbzCl (2.91 g, 17.0 mmol), and the mixture was stirred at rt for 12 h. On completion, the mixture was extracted with DCM (2×100 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM:MeOH=10:1) to give the title compound (4.00 g, 67% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.38-7.33 (m, 5H), 5.56 (s, 1H), 5.11 (s, 2H), 3.73-3.42 (m, 23H). |
46% | With triethylamine In tetrahydrofuran at 0℃; Inert atmosphere; | 31 Preparation of Compound 21b Preparation of Compound 21b To a solution of compound 21a (8.24 g, 29.2 mmol) in THF (190 mL) was added triethylamine (6.1 mL, 43.9 mmol) and benzyl chloroformate (4.6 mL 32.2 mmol) at 0 °C under N2. The reaction mixture was concentrated and the crude product was purified by column chromatography to produce the compound 21b (5.59 g, 46 %). 1H- MR (400 MHz, CDCI3) δ 7.45-7.20 (m, 5H), 5.61 (br s, 1H), 5.09 (s, 2H), 3.85-3.50 (m, 22H), 3.39 (m, 2H). |
46% | With triethylamine In tetrahydrofuran at 0℃; Inert atmosphere; | 31 Preparation of Compound 21b To a solution of compound 21a (8.24 g, 29.2 mmol) in THF (190 mL) was added triethylamine (6.1 mL, 43.9 mmol) and benzyl chloroformate (4.6 mL 32.2 mmol) at 0 °C under N2. The reaction mixture was concentrated and the crude product was purified by column chromatography to produce the compound 21b (5.59 g, 46 %). 1H-NMR (400 MHz, CDC13) δ 7.45-7.20 (m, 5H), 5.61 (br s, 1H), 5.09 (s, 2H), 3.85-3.50 (m, 22H), 3.39 (m, 2H). |
With triethylamine In dichloromethane at 20℃; for 0.5h; | 3.1 Step 1: Synthesis of benzyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate (2) 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol (1 g, 3.55 mmol) and TEA (719.33 mg, 7.11 mmol, 0.989 mL) in DCM (10 mL) to the mixture was added benzyl chloroformate (666.98 mg, 3.91 mmol, 0.5556 mL). The mixture was stirred at 20° C. for 0.5 hours. LCMS showed the main peak of the desired mass. The mixture was washed with water (20 mL), The organic layer was dried over anhydrous Na2SO4 and concentrated to give the title compound (1.48 g, crude) as a colorless oil, It was used directly in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 120 °C 2: dmap; triethylamine / dichloromethane / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: N,N-dimethyl-formamide / 120 °C 2: silver(l) oxide / 72 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 120 °C 2: dmap; triethylamine / dichloromethane / 20 °C 3: potassium carbonate / N,N-dimethyl-formamide / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide / 120 °C 2: dmap; triethylamine / dichloromethane / 20 °C 3: potassium carbonate / N,N-dimethyl-formamide / 70 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | In N,N-dimethyl-formamide at 120℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.14 g | With hydrogenchloride In ethanol at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: C38H42N3O8S2Si(1+)*C2F3O2(1-) With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 20h; Stage #2: 3,6,9,12,15,18-hexaoxa-1-octadecyl amine With N-ethyl-N,N-diisopropylamine In water at 20℃; for 15h; | 9 Steps (a) and (b) SiRpH5 (15 mg, 17.2 tmol), N-hydroxysuccinimide (2.2 mg, 18.9 tmol), EDC hydrochloride (3.6 mg, 18.9 mmol), and DMF (2 mL) were added to a flask; DIPEA (6.6 tL, 37.8 tmol) was then added, and stirred for 20 hours at room temperature. The reaction solution was purified by HPLC (eluent, from 28% acetonitrile/0.1% trifluoroacetic acid/water (0 mm) to 60% acetonitrile/0.1% TFAwater (20 mm); flow rate=25.O mL/min), and the solvent was distilled oil under reduced pressure. NH2-PEG5-OH (4.9 mg, 13.7 tmol), DIPEA (25 pL, 0.14 mmol), and water (50 pL) were added to the residue, and stirred for 15 hours at room temperature. The reaction solution was purified by HPLC (eluent, from 28% acetonitrile/0.1% trifluoroacetic acid water (0 mm) to 60% acetonitrile/0.1% TFAwater (20 mm); flow rate=25.0 mL/min), and the solvent was distilled off under reduced pressure (SiRpH5-PEG5-OH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium hydrogencarbonate In tetrahydrofuran at 20℃; for 3h; | 1 Step 1-tert-butyl tert-butyl (17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)carbamate To a stirred solution of 17-amino-3,6,9,12,15-pentaoxaheptadecan-1-ol (4.0 g, 14.22 mmol, CAS39160-70-8) in THF (50 mL) was added (Boc)2O (3.72 g, 17.06 mmol) and NaHCO3 (saturated solution, 2 mL) at rt. The reaction mixture was stirred at rt for 3 h. The mixture was concentrated in vacuo and the residue was purified by column to give the desired compound (4.96 g, yield, 73%) as a yellow oil. LC-MS (ESI+): m/z 382.43 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; acetonitrile / 12 h / 20 °C 2: 10 wt% Pd(OH)2 on carbon / ethyl acetate / 12 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In ethanol at 78℃; for 4h; | 6 Synthesis procedure and characterization: 3-nitrorhodamine (2 mmol, 0.974 g) and amino hexaethylene glycol (2 mmol, 0.562 g) were dissolved in absolute ethanol (5 mL) and heated to reflux at 78 ° C.After stirring for 4 hours, the solvent was evaporated under reduced pressure.The product was purified by column chromatography (silica gel, methylene chloride/methanol, 10:1 v/v) to afford a pale yellow viscous liquid (1.42 g, 95%). The liquid product was then completely dissolved in methanol (5 mL), stirred under a hydrogen atmosphere and palladium on carbon (10% wt) for 1 hour, filtered and filtered.After the solvent was evaporated under reduced pressure to give the final product as a white viscous liquid (1.35g, 99%). |
95% | In ethanol at 78℃; for 4h; | 6 Synthesis steps and characterization: 3-nitrorhodamine (2 mmol, 0.974 g) andAminohexaethylene glycol(2mmol, 0.562g)Absolute ethanol(5mL), heated to 78 ° C under reflux, stirred for 4 hours and evaporated the solvent under reduced pressure. The product was passed through column chromatography (silica gel, dichloromethane / methanol, 10: 1 v / v)The resulting pale yellow viscous liquid was isolated and purified (1.42 g, 95%).Then, the liquid product was completely dissolved in methanol (5 mL), and stirred under a hydrogen atmosphere and palladium on carbon (10% wt) for 1 hour. The solution was filtered with suction and the filtrate was evaporated under reduced pressure to obtain the final white viscous liquid product (1.35 g, 99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In ethanol at 78℃; for 4h; | 1 Synthesis steps and characterization: 3-Nitrorhodamine (2 mmol, 0.974 g)And aminohexa polyethylene glycol (2 mmol, 0.562 g) were dissolved in absolute ethanol (5 mL),Heated to 78 ° C and refluxed,After stirring for 4 hours, the solvent was evaporated under reduced pressure.The product was separated and purified by column chromatography (silica gel, dichloromethane / methanol, 10: 1 v / v) to obtain a pale yellow viscous liquid (1.42 g, 95%).The liquid product was then completely dissolved in methanol (5 mL),Stir for 1 hour under hydrogen atmosphere and palladium-carbon (10% wt) catalyst.The filtrate was collected by suction filtration, and the solvent was distilled off under reduced pressure to obtain the final white viscous liquid product P1 (1.35 g, 99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In ethanol at 78℃; for 4h; | 7 Synthesis steps and characterization: 3-nitrorhodamine (0.24g, 0.5mmol) andAminohexapolyethylene glycol monomethyl ether(0.14g, 0.5mmol) was dissolved in absolute ethanol (8mL), heated to 78 ° C and refluxed. After stirring for 4 hours, the solvent was evaporated under reduced pressure. The residue was subjected to column chromatography (silica gel, ethyl acetate / methanol, 30: 1v / v) Isolated a viscous liquid (0.34 g, 90%). It was all dissolved in methanol (5 mL) and 20 mg of 10% palladium on carbon was added for catalytic reduction under a hydrogen atmosphere. The reaction mixture was suction filtered, and the filtrate was evaporated under reduced pressure to remove the solvent. The product was separated by column chromatography (silica gel, ethyl acetate / methanol, 20: 1 v / v) to obtain a viscous liquid P7 (0.32 g, 96%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 130℃; | ||
With triethylamine In 1-methyl-pyrrolidin-2-one at 90℃; for 24h; | 4.1 Rucaparib-PEG5-pomalidomide (9a) Step 1. Synthesis of hydroxy-PEG5-pomalidomides (lOe) To a solution of 3 (30.0 mg, 108.6 miho, 1.0 equiv) and amino-PEG6-alcohol (60.1 mg, 217.2 mhio. 2.0 equiv) in /V-methyl-2-pyrrolidone (2 mL) was added triethylamine (33.2 mg, 325.8 mhio. 3.0 equiv). After stirring at 90 °C for 24 h, the mixture was concentrated and purified by silica gel flash column chromatography to give lOe as a yellow solid. NMR (400 MHz, CDCb) d 7.47 (dd, J = 8.5, 7.1 Hz, 1H), 7.08 (d, J = 7.1 Hz, 1H), 6.90 (d, J = 8.5 Hz, 1H), 6.48 (t, J = 5.4 Hz, 1H), 4.90 (dd, J = 11.7, 5.3 Hz, 1H), 3.78-3.53 (m, 22H), 3.45 (dd, J = 10.8, 5.4 Hz, 2H), 2.88-2.68 (m, 3H), 2.14-2.05 (m, 1H); 13C NMR (101 MHz, CDCb) d 171.6, 169.3, 168.7, 167.7, 146.9, 136.1, 132.6, 116.9, 111.7, 110.4, 72.6, 70.9, 70.7, 70.6, 70.6, 70.5, 70.3, 69.5, 61.7, 49.0, 42.5, 31.5, 22.9; MS (ESI)+ calculated for C25H36N3O10 (M+H)+ 538.2, found 538.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 130 °C 2: Dess-Martin periodane / dichloromethane / 20 °C 3: sodium cyanoborohydride; acetic acid / methanol |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dimethyl sulfoxide / 130 °C 2: Dess-Martin periodane / dichloromethane / 20 °C | ||
Multi-step reaction with 2 steps 1: triethylamine / 1-methyl-pyrrolidin-2-one / 24 h / 90 °C 2: Dess-Martin periodane / dichloromethane; water / 16 h / 0 - 23 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
273 mg | With triethylamine In dichloromethane; N,N-dimethyl-formamide at 25℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine In N,N-dimethyl-formamide Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With pyridine at 125℃; for 24h; Inert atmosphere; | 4.S1 Synthesis of compound I Add compound PMCDA (322 mg, 1 mmol, 1.0 eq.) and compound H (232 mg, 1.2 mmol, 1.2 eq.) in a 25 mL round bottom flask, and then add 10 mL of anhydrous pyridine, under nitrogen protection, 125 React at for 24h, cool to room temperature, add 30mL of dichloromethane to it, wash with 2M hydrochloric acid 3 times, 100mL each time, then wash with saturated brine, and dry with anhydrous magnesium sulfate.The spin-dried compound I was a red solid with a yield of 95%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; Inert atmosphere; | General procedure: To a stirred mixture of 2,5-dioxopyrrolidin-1-yl 2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxy}acetate (2.00g, 4.65 mmol, 1.00 equiv) and 2-{2-[2-(2-aminoethoxy)ethoxy]-ethoxy}ethanol (0.90 g, 4.65 mmol, 1.00 equiv) in DMF (20mL) was added DIEA (1.20 g, 9.27 mmol, 1.99 equiv) dropwiseat 0 °C under a nitrogen atmosphere. The resulting mixture wasstirred overnight at room temperature. The reaction mixture waspurified by reverse-phase flash chromatography [column, C18silica gel; mobile phase, acetonitrile in water (0.1% formic acid),0% to 70% gradient in 10 min; detector, UV 254 nm] to give 2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxy}-N-(2-{2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}ethyl)acetamide(1.1 g, 46%) as a light yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: triethylamine / methanol / 18 h / 20 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 0 - 20 °C / Inert atmosphere 3: potassium carbonate / acetonitrile / 18 h / 90 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: triethylamine / methanol / 18 h / 20 °C / Inert atmosphere 2: sodium hydroxide / tetrahydrofuran / 18 h / 20 °C / Inert atmosphere 3: potassium carbonate / acetonitrile / 18 h / 90 °C / Inert atmosphere | ||
Multi-step reaction with 3 steps 1: triethylamine / methanol / 18 h / 20 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 0 - 20 °C / Inert atmosphere 3: potassium carbonate / acetonitrile / 18 h / 90 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: triethylamine / methanol / 18 h / 20 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 0 - 20 °C / Inert atmosphere 3: potassium carbonate / acetonitrile / 18 h / 90 °C / Inert atmosphere 4: dichloromethane / 18 h / 20 °C / Inert atmosphere | ||
Multi-step reaction with 4 steps 1: triethylamine / methanol / 18 h / 20 °C 2: sodium hydroxide / tetrahydrofuran / 18 h / 0 - 20 °C / Inert atmosphere 3: potassium carbonate / acetonitrile / 18 h / 90 °C / Inert atmosphere 4: dichloromethane / 18 h / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68.6% | With Caswell No. 744A In N,N-dimethyl-formamide at 50℃; for 8h; Inert atmosphere; | 1 To a stirred solution of 17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl 4- methylbenzenesulfonate, 60 (2.9 g, 6.64 mmol) in dry DMF (20 mL) was added sodium azide (648 mg, 9.96 mmol) under an atmosphere of nitrogen. The resulting solution was heated to 50 °C and stirred for 8 h, at which point it was cooled to ambient temperature and quenched with ice-water (20 mL) and extracted with dichloromethane (3 x 25 mL). The combined organic layers were washed with brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The remaining residue was purified by flash chromatography (60-120 mesh, 50-100% EtOAc in petroleum ether). Fractions containing the desired product were combined and concentrated under reduced pressure to afford 17-azido- 3,6,9,12,15-pentaoxaheptadecan-1-ol, 61 (1.4 g, 68.6%) as a pale-yellow liquid. |
68.6% | With Caswell No. 744A In N,N-dimethyl-formamide at 50℃; for 8h; Inert atmosphere; | 1 To a stirred solution of 17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl 4- methylbenzenesulfonate, 60 (2.9 g, 6.64 mmol) in dry DMF (20 mL) was added sodium azide (648 mg, 9.96 mmol) under an atmosphere of nitrogen. The resulting solution was heated to 50 °C and stirred for 8 h, at which point it was cooled to ambient temperature and quenched with ice-water (20 mL) and extracted with dichloromethane (3 x 25 mL). The combined organic layers were washed with brine (25 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The remaining residue was purified by flash chromatography (60-120 mesh, 50-100% EtOAc in petroleum ether). Fractions containing the desired product were combined and concentrated under reduced pressure to afford 17-azido- 3,6,9,12,15-pentaoxaheptadecan-1-ol, 61 (1.4 g, 68.6%) as a pale-yellow liquid. |
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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