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CAS No. : | 4741-99-5 | MDL No. : | MFCD00008174 |
Formula : | C7H20N4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | UWMHHZFHBCYGCV-UHFFFAOYSA-N |
M.W : | 160.26 | Pubchem ID : | 78479 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 8 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 4.0 |
Molar Refractivity : | 46.78 |
TPSA : | 76.1 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -8.81 cm/s |
Log Po/w (iLOGP) : | 1.61 |
Log Po/w (XLOGP3) : | -2.16 |
Log Po/w (WLOGP) : | -1.53 |
Log Po/w (MLOGP) : | -0.77 |
Log Po/w (SILICOS-IT) : | -0.65 |
Consensus Log Po/w : | -0.7 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | 1.06 |
Solubility : | 1820.0 mg/ml ; 11.4 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 1.09 |
Solubility : | 1980.0 mg/ml ; 12.4 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | -2.09 |
Solubility : | 1.31 mg/ml ; 0.00817 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 1.46 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | 2735 |
Hazard Statements: | H314 | Packing Group: | Ⅲ |
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 |
---|---|---|
41% | In ethanol for 408h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In acetonitrile; at 0℃; for 2h; | A solution of 5.37 g (62.4 mmol) of butanedione in 30 ml of acetonitrile is slowly added dropwise to a solution of 10.00 g (62.4 mmol) of commercial N,N'-bis (2-aminoethyl)-1,3-propanediamine in 100 ml of acetonitrile at 0 C. The mixture is maintained at this temperature for two hours. After evaporating the solvent, compound 1 is isolated quantitatively in the form of a yellow solid and is used for the following stage without subsequent purification.13C NMR spectrometry (125 MHz, CDCl3, delta in ppm) 10.7, 18.3, 23.3, 39.2, 42.0, 45.6, 46.6, 49.0, 51.1, 68.1, 73.3.Mass spectrometry: (MALDI-TOF) m/z =210 M+?. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In chloroform; for 72h;Heating / reflux; | Bis-l,3-{(5,6-dihydro-5,l 1-diketo-l lH-indeno[l,2-c]isoquinoline)-(6- ethyl-terL-BOCamino)}?ropane (13a). N,?r'-Bis(2-aminoethyl)-l ,3-propanediamine (1 Ig) (0.10 g, 0.62 mmol) was added to a stirred solution of indenobenzopyran 4d (0.34 g, 1.37 mmol) in C?CI3 (150 mL) and the reaction mixture was stirred under reflux for 72 h, providing bisindenoisoquinoline 12g as a crude intermediate. After allowing the reaction mixture to cool to room temperature, Et3N (0.35 mL, 2.50 mmol) and BOC2O (0.34 g, 1.56 mmol) were added, and the reaction mixture was stirred at room temperature for 8 h. The crude reaction mixture was purified by flash column chromatography (Si?2/20% EtOAc in hexane, then 1-5% MeOH in CHCI3) to provide Boc-protected bisindenoisoquinoline 13a (380 mg, 74%) as an orange solid: mp 238-2400C. 1H NMR (CDCl3) ? 8.63 (d, J= 8.0 Hz, 2 H), 8.16 (d, J= 7.4 Hz, 2 H), 7.65-7.58 (m, 5 H), 7.53-7.45 (m, 2 H), 7.38-7.29 (m, 5 H), 4.63 (bs, 4 H), 3.62 (bs, 4 H), 3.32 (bs, 4 H), 1.90 (bs, 2 H), 1.41 (s, 18 H); ESIMS m/z (rel intensity) 821 (MH+, 10), 721 (MH+-BoC, 100). Anal. Calcd S^r C49H48N4O8: C, 71.69; H, 5.89; N, 6.82. Found: C3 71.35; H, 5.99; N, 6.68 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In water; at 0 - 20℃; for 11h; | 9.04 g (62.4 mmol) of a 40% by weight aqueous glyoxal solution are slowly added dropwise to a solution of 10.00 g (62.4 mmol) of N,N'-bis(2-aminoethyl)-1,3-pro-panediamine in 30 ml of water at 0 C. The mixture is maintained at this temperature for 1 hour and then stirred at ambient temperature for 10 hours. After evaporation of the water, compound 12 is isolated quantitatively in the form of a pale yellow solid and is used for the following stage without subsequent purification.13C NMR spectrometry (50 MHz, CDCl3, delta in ppm) 19.8, 54.0-55.5 (broad), 67.3, 77.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 90 percent / ethanol / 3 h / 0 °C 2: 55 percent / cesium carbonate / acetonitrile / 96 h / 40 °C 3: hydrochloric acid / H2O / 6 h / 60 °C | ||
Multi-step reaction with 3 steps 1: 90 percent / ethanol / 3 h / 0 °C 2: 85 percent / cesium carbonate / acetonitrile / 72 h / 40 °C 3: hydrochloric acid / H2O / 6 h / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; sodium hydrogencarbonate; magnesium; In methanol; ethanol; water; N,N-dimethyl-formamide; benzene; | EXAMPLE 2 [2-(methylethylamino)ethyl](3-[2-(methylamino)ethyl]amino}propyl)amine [FIG. 2]. A mixture of 0.37 g (0.0155 mol) of magnesium turnings, 5.0 g (0.031 mol) of 1,3-bis-[(2'-aminoethyl)-amino]propane, 50 mL of benzene and 3.76 g (0.047 mol) of acetyl chloride is heated under reflux for 2 h. The reaction mixture is cooled in an ice bath and the liquid portion is decanted into a separatory funnel. The residue in the flask is washed twice with 50 mL portions of ether, and the ethereal solution is poured over ice. The ether-water mixture is then added to the benzene solution in the separatory funnel and separated. The organic phase is washed once with 50 mL of 5% sodium bicarbonate and once with water and dried over CaCl2. The solution is filtered and used without further purification. A magnetically stirred mixture of 5.0 g (8.67 mmol) of the acetylated 2,3,2-tetramine prepared above and 2.0 g (80.7 mmol) of sodium hydride in 75 mL of N,N-dimethylformamide was heated at 60 C. under N2 for 3 h. The resultant mixture was treated with 19.8 g (0.164 mol) of iodomethane and stirred at 50 C. After 24 h at 50 C., the reaction was quenched by the addition of 95% EtOH. Volatiles were removed at reduced pressure and 50 mL of water was added to the residue. The product was extracted with three 50 mL portions of chloroform. The combined organic extracts were successively washed with water and NaCl, dried over anhydrous sodium sulfate, and concentrated to give 6.3 g of yellowish oil. The oil was purified by flash chromatography with 1:4 hexanes-ethyl acetate as the eluent to give acetylated [2-(methylethylamino)ethyl](3-[2-(methylamino)ethyl]amino}propyl)amine as an oil. A stirred solution of 3.0 g (4.54 mmol) of acetylated [2-(methylethylamino)ethyl](3-[2-(methylamino)ethyl]amino}propyl)amine, 10.0 g (0.178 mol) of potassium hydroxide, 70 mL of methanol and 15 mL of water was heated under reflux for 24 h. The methanol was removed at reduced pressure and the product was extracted into 2*50 mL of ether. The combined extracts were washed with NaCl, dried over sodium sulfate and concentrated under vacuum. The crude mixture was purified by flash chromatography with 5:1 hexanes-ethyl acetate as the eluent. After evaporation of the solvents, 0.79 g (71%) of the product was obtained as a colorless oil. Mass spectral analysis showed a m/e=244. 1H NMR (CDCl3): delta1.03 (12 H, d), 1.26 (6H, s), 1.60 (2H, quin), 2.60 (4H, t), 2.71 (8H, t), 3.23 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; potassium chloride; In ethanol; | EXAMPLE 1 1,3-bis-[(2'-aminoethyl)-amino]propane [FIG. 1]. A mixture of 15 g of 1,3-dibromopropane and 50 mL of absolute EtOH was added slowly to 25 g of 1,2-diaminoethane hydrate. The mixture immediately became warm. It was then heated to 50 C. for 1 hour, 20 g of KCl added and the heating continued for 30 minutes. The mixture was filtered from the KBr and distilled at reduced pressure. The residue formed two layers that were separated. The top layer was distilled and the product had a b.p. of 115-116 C., (1 mm). The compound was further purified by converting the free amine to its tetrahydrochloride salt by addition of 6M. HCl. The melting point of the salt was 278-283 C. It was converted back to its free amine by treatment with NH4OH. Mass spectral analysis showed a m/e=160. 1H NMR (CDCl3): delta 1.26 (6H, s), 1.60 (2H, quin), 2.60 (4H, t), 2.71 (8H, t). | |
With ammonium hydroxide; potassium chloride; In ethanol; | EXAMPLE 1 1,3bis-[(2'-aminoethyl)-amino]propane [FIG. 1] A mixture of 15 g of 1,3-dibromopropane and 50 mL of absolute EtOH was added slowly to 25 g of 1,2 diaminoethane hydrate. The mixture immediately became warm. It was then heated to 500C for 1 hour, 20 g of KCl added and the heating continued for 30 minutes. The mixture was filtered from the KBr and distilled at reduced pressure. The residue formed two layers that were separated. The top layer was distilled and the product had a b.p. of 115-116 C., (1 mm). The compound was further purified by converting the free amine to its tetrahydrochloride salt by addition of 6M. HCl. The melting point of the salt was 278-283 C. It was converted back to its free amine by treatment with NH4OH. Mass spectral analysis showed a m/e=160. 1H NMR (CDCl3): delta 1.26 (6H, s), 1.60 (2H, quin), 2.60 (4H, t), 2.71 (8H, t). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In pyridine; dichloromethane; | A. Synthesis of 1,4,8,11-Tetra(p-toluenesulfonyl)-<strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong> To a stirred solution of p-toluenesulfonyl chloride (262 g, 1.37 mole) in anhydrous pyridine (600 ml) at 5 C. was added a solution of <strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong> (49.1 g, 0.306 mole) in anhydrous pyridine (200 ml) under a dry argon atmosphere, maintaining the temperature <20 C. The addition required 1 h. The mixture was stirred overnight at room temperature. H2 O (1.5 l) was slowly added to the cooled (ice bath) mixture. The resulting oil was dissolved in CH2 Cl2, separated from the aqueous layer. The CH2 Cl2 layer was washed with 5% HCl and H2 O and dried (MgSO4). The solvent was removed in vacuo to give an oil which solidified on standing. The resulting solid was ground to a powder and dried in vacuo to give 186 g (78% yield) of the crude product: 1 H NMR (CDCl3) delta1.98 (quint, J=7.3 Hz, 2 H), 2.40 (s, 6 H), 2.42 (s, 6 H), 3.11 (t, J=7.3 Hz, 4 H), 3.17 (s, 8 H), 5.76 (t, J=6.0 Hz, 2 H), 7.29 (m, 8 H), 7.64 (d, J=8.3 Hz, 4 H), 7.75 (d, J=8.3 Hz, 4 H). |
78% | In pyridine; dichloromethane; | A. Synthesis of 1,4,8,11-Tetra(p-toluenesulfonyl]-<strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong> To a stirred solution of p-toluenesulfonyl chloride (262 g, 1.37 mole) in anhydrous pyridine (600 ml) at 5 C. was added a solution of <strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong> (49.1 g, 0.306 mole) in anhydrous pyridine (200 ml) under a dry argon atmosphere, maintaining the temperature <20 C. The addition required 1 h. The mixture was stirred overnight at room temperature. H2 O (1.5 1) was slowly added to the cooled (ice bath) mixture. The resulting oil was dissolved in CH2 Cl2, separated from the aqueous layer. The CH2 Cl2 layer was washed with 5% HCl and H2 O and dried (MgSO4). The solvent was removed in vacuo to give an oil which solidified on standing. The resulting solid was ground to a powder and dried in vacuo to give 186 g (78% yield) of the crude product: 1 H NMR (CDCl3) delta1.98 (quint, J=7.3 Hz, 2 H), 2.40 (s, 6 H), 2.42 (s, 6 H), 3.11 (t, J=7.3 Hz, 4 H), 3.17 (s, 8 H), 5.76 (t, J=6.0 Hz, 2 H), 7.29 (m, 8 H), 7.64 (d, J=8.3 Hz, 4 H), 7.75 (d, J=8.3 Hz, 4 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28.3% | In ethanol; | (1) A mixture of 37.2 grams (0.231 mole) of diethyl malonate and 37.0 grams (0.231 mole) of <strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong> was refluxed in about 1.5 liters of ethanol for 4 days. Thereafter the ethanol was distilled away to adjust the amount to about 500 milliliters and crystals precipitated were recrystallized from ethanol. Thus, 14.9 grams of colorless prism crystals, 1,5,8,12-tetraaza-2,4-dioxycyclotetradecane was obtained. The yield was 28.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; N-methymorpholine; at 20 - 115℃; for 2.33333h; | A solution of N,N-bis(aminoethyl)-1,3-propanediamine (also: <strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong>, 0.081 ml, 0.47 mmole) in 5 ml dioxane was slowly added to a solution of 3-bromo-1,8-naphthalic anhydride (0.267 gm, 0.93 mmole) in 1.2 ml NMM. The reaction was stirred at room temperature under nitrogen for 5 minutes, then heated at 38 C for 45 minutes, the heat was increased slowly to 115 C and held for 1.5 hours. The mixture was cooled, filtered, concentrated under vacuum, dissolved in a minimum of dichloromethane, and purified by silica gel chromatography to give the bis TFA salt of N, N'-(bis-aminoethyl-1,3-propanediamine)-bis-3-bromo- 1,8 naphthalimide 18 as a white solid. MS m/z 679 (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N-methymorpholine; at 20 - 120℃; for 3.08333h; | A solution of N,N-bis(aminoethyl)-1,3-prorhoanediamine (0.91 gm, 5.29 mmole) in 5 ml N- methylmorpholine (NMM) was added to a solution of 4-nitro-1,8-naphthalic anhydride (2.54 gm, 9.92 mmole) in 10 ml NMM. The reaction was stirred at room temperature under nitrogen for 5 minutes, then heated at 38 C for one hour, then at 120 C (reflux) for 2 hours. The mixture was filtered hot, concentrated under vacuum, dissolved in a minimum of dichloromethane, and purified by silica gel chromatography to give N, N'-(bis- aminoethyl-1,3-propanediamine)-bis-4-nitro-1,8 naphthalimide 16a. MS mlz 611 (M + H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N-methymorpholine; ethanol; at 20 - 115℃; for 2.33333h; | A solution of N,N-bis(aminoethyl)-1,3-propanediamine (also: <strong>[4741-99-5]1,4,8,11-tetraazaundecane</strong>, 0.87 ml, 5.03 mmole) in 2 ml ethanol was slowly added to a solution of 4-chloro-1,8-naphthalic anhydride (2.35 gm, 10.10 mmole) in 12 ml NMM. The reaction was stirred at room temperature under nitrogen for 5 minutes, then heated at 38 C for 45 minutes, the heat was increased slowly to 115 C and held for 1.5 hours. The mixture was cooled, filtered, concentrated under vacuum, dissolved in a minimum of dichloromethane, and purified by silica gel chromatography to give the bis TFA salt of N, N'-(bis-aminoethyl-1,3-propanediamine)-bis-4-chloro- 1,8 naphthalimide 17 as a bright yellow solid. MS m/z 589 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium borohydrid; potassium carbonate; In potassium hydroxide; ethanol; water; acetonitrile; | Preparation of 4,11-dimethyl-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadecane To a 250 mL, 3 necked round bottom flask, equipped with a thermometer, nitrogen inlet, and magnetic stirrer is added N,N'-bis(2-aminoethyl)-1,3-propanediamine (5.00 g, 31.3 mmol) and absolute ethanol (100 mL). The solution is stirred under argon and cooled to 15 C. using an ice bath. Aqueous glyoxal (4.78 g., 33 mmol, 40% in water) is added dropwise with stirring. Upon completion of the addition, the solution is concentrated under reduced pressure to yield a clear, colorless oil. The isolated oil has the formula: and is obtained in 100% yield (6.0 g). Cyclic amine 1 (6.0 g) is suspended in acetonitrile (100 mL). Potassium carbonate (25 g) and 1,3-propanediol ditosylate (12.61 g, 32.8 mmol) are added. The solution is stirred vigorously at RT overnight. The reaction is then warmed to 70 C. and filtered hot with glass fiber filter paper and vacuum filtration. The resulting solid is washed with acetonitrile (100 mL). The acetonitrile filtrate is concentrated under reduced pressure to yield a light green oil having the formula: and is obtained in 100% yield (7.0 g). The tetraamine 2, (7.0 g) is dissolved in acetonitrile (150 mL). Methyl sulfate (2.5 equiv.) is added, the reaction warmed to 65 C. and stirred for 9 days. The solvent is removed under reduced pressure to yield a brown oil having the formula: and is obtained in approximately 85% yield. Distilled water (25 mL) and potassium carbonate (13.8 g) are added to a 250 mL round bottomed flask. Absolute ethanol (75 mL) is added and the resulting biphasic solution is stirred and heated to 60 C. with an oil bath. Sodium borohydride (1.60 g., 42.3 mmol) and 3 (10.0 g., 21.1 mmol) was added to the solution. The reaction is stirred at 60 C. for 75 minutes. The reaction mixture is placed in a separatory funnel and the ethanol layer collected. The solvent is then removed under reduced pressure, the resulting tan solid/oil is dissolved in 5N KOH (5 mL) and extracted with toluene (2*50 mL). The toluene is removed under reduced pressure to yield 4,11-dimethyl-1,4,8,11-tetraaza-bicyclo[6.6.2]hexadecane having the formula: as an oil, in 95% yield (5.2 g) after distillation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In N,N-dimethyl-formamide; at 100℃; for 0.25h;Microwave irradiation; | General procedure: To a solution of anhydride 10 (0.39 mmol) in DMF (6 mL), was added N,N'-bis(2-aminoethyl)-1,3-propanediamine 6 (0.033 mL, 0.19 mmol). The mixture was stirred under microwave heating (10a: 450 W, 100 C; 10b: 600 W, 120 C; 10c: 450 W, 130 C) for 15 min. Starting from 10a,b, the mixture was then diluted with Et2O (15 mL) and brine (10 mL). A solid was formed, filtered and washed with Et2O to give pure compounds 11a,b. Starting from 10c, a solid was directly formed in the reaction mixture which was collected and washed with Et2O affording pure 11c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
24% | In N,N-dimethyl-formamide; at 120℃; for 0.25h;Microwave irradiation; | General procedure: To a solution of anhydride 10 (0.39 mmol) in DMF (6 mL), was added N,N'-bis(2-aminoethyl)-1,3-propanediamine 6 (0.033 mL, 0.19 mmol). The mixture was stirred under microwave heating (10a: 450 W, 100 C; 10b: 600 W, 120 C; 10c: 450 W, 130 C) for 15 min. Starting from 10a,b, the mixture was then diluted with Et2O (15 mL) and brine (10 mL). A solid was formed, filtered and washed with Et2O to give pure compounds 11a,b. Starting from 10c, a solid was directly formed in the reaction mixture which was collected and washed with Et2O affording pure 11c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In N,N-dimethyl-formamide; at 130℃; for 0.0833333h;Microwave irradiation; | General procedure: N,N'-Bis-(2-Aminoethyl)-1,3-propanediamine (6) (0.03 mL, 0.17 mmol) and anhydride 5e or h (0.34 mmol) were dissolved in DMF (8 mL). The mixture was stirred under microwave heating (130 C, 450 W) in the presence of a Weflon stirrer for 5 min. The mixture was cooled at room temperature and diluted with a solvent (5e: AcOEt, 15 mL; 5h: Et2O, 15 mL) and brine (10 mL). The organic layer was separated, washed with water, dried over anhydrous Na2SO4 and filtered. Pure compound 7e was obtained after crystallization. Instead, when the ethereal solution was concenterd, a yellow solid was separated corresponding to pure 7h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | In N,N-dimethyl-formamide; at 130℃; for 0.25h;Microwave irradiation; | General procedure: To a solution of anhydride 10 (0.39 mmol) in DMF (6 mL), was added N,N'-bis(2-aminoethyl)-1,3-propanediamine 6 (0.033 mL, 0.19 mmol). The mixture was stirred under microwave heating (10a: 450 W, 100 C; 10b: 600 W, 120 C; 10c: 450 W, 130 C) for 15 min. Starting from 10a,b, the mixture was then diluted with Et2O (15 mL) and brine (10 mL). A solid was formed, filtered and washed with Et2O to give pure compounds 11a,b. Starting from 10c, a solid was directly formed in the reaction mixture which was collected and washed with Et2O affording pure 11c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In dichloromethane; at 100℃; for 0.25h;Microwave irradiation; | General procedure: Amine 6 (0.025 mL, 0.15 mmol) or 8 (0.031 mL, 0.15 mmol) was added to a solution of anhydride 5 (0.3 mmol) in CH2Cl2 (3 mL). The mixture was stirred under microwave heating (100 C, 450 W) in the presence of a Weflon stirrer (7a-d,f,g, 9: 15 min). The mixture was cooled at room temperature and water (5 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated and the residue was purified by crystallization. In case of 5g, a solid was formed during the reaction which was filtered from the hot solution, washed with CH2Cl2 to give pure compound 7g. Pure compound 9 was directly obtained from the reaction mixture by addition of Et2O and washing the solid with the same solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In dichloromethane; at 100℃; for 0.25h;Microwave irradiation; | General procedure: Amine 6 (0.025 mL, 0.15 mmol) or 8 (0.031 mL, 0.15 mmol) was added to a solution of anhydride 5 (0.3 mmol) in CH2Cl2 (3 mL). The mixture was stirred under microwave heating (100 C, 450 W) in the presence of a Weflon stirrer (7a-d,f,g, 9: 15 min). The mixture was cooled at room temperature and water (5 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated and the residue was purified by crystallization. In case of 5g, a solid was formed during the reaction which was filtered from the hot solution, washed with CH2Cl2 to give pure compound 7g. Pure compound 9 was directly obtained from the reaction mixture by addition of Et2O and washing the solid with the same solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | In dichloromethane; at 100℃; for 0.25h;Microwave irradiation; | General procedure: Amine 6 (0.025 mL, 0.15 mmol) or 8 (0.031 mL, 0.15 mmol) was added to a solution of anhydride 5 (0.3 mmol) in CH2Cl2 (3 mL). The mixture was stirred under microwave heating (100 C, 450 W) in the presence of a Weflon stirrer (7a-d,f,g, 9: 15 min). The mixture was cooled at room temperature and water (5 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated and the residue was purified by crystallization. In case of 5g, a solid was formed during the reaction which was filtered from the hot solution, washed with CH2Cl2 to give pure compound 7g. Pure compound 9 was directly obtained from the reaction mixture by addition of Et2O and washing the solid with the same solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In dichloromethane; at 100℃; for 0.25h;Microwave irradiation; | General procedure: Amine 6 (0.025 mL, 0.15 mmol) or 8 (0.031 mL, 0.15 mmol) was added to a solution of anhydride 5 (0.3 mmol) in CH2Cl2 (3 mL). The mixture was stirred under microwave heating (100 C, 450 W) in the presence of a Weflon stirrer (7a-d,f,g, 9: 15 min). The mixture was cooled at room temperature and water (5 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated and the residue was purified by crystallization. In case of 5g, a solid was formed during the reaction which was filtered from the hot solution, washed with CH2Cl2 to give pure compound 7g. Pure compound 9 was directly obtained from the reaction mixture by addition of Et2O and washing the solid with the same solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In dichloromethane; at 100℃; for 0.25h;Microwave irradiation; | General procedure: Amine 6 (0.025 mL, 0.15 mmol) or 8 (0.031 mL, 0.15 mmol) was added to a solution of anhydride 5 (0.3 mmol) in CH2Cl2 (3 mL). The mixture was stirred under microwave heating (100 C, 450 W) in the presence of a Weflon stirrer (7a-d,f,g, 9: 15 min). The mixture was cooled at room temperature and water (5 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated and the residue was purified by crystallization. In case of 5g, a solid was formed during the reaction which was filtered from the hot solution, washed with CH2Cl2 to give pure compound 7g. Pure compound 9 was directly obtained from the reaction mixture by addition of Et2O and washing the solid with the same solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In dichloromethane; at 100℃; for 0.25h;Microwave irradiation; | General procedure: Amine 6 (0.025 mL, 0.15 mmol) or 8 (0.031 mL, 0.15 mmol) was added to a solution of anhydride 5 (0.3 mmol) in CH2Cl2 (3 mL). The mixture was stirred under microwave heating (100 C, 450 W) in the presence of a Weflon stirrer (7a-d,f,g, 9: 15 min). The mixture was cooled at room temperature and water (5 mL) was added. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The solvent was evaporated and the residue was purified by crystallization. In case of 5g, a solid was formed during the reaction which was filtered from the hot solution, washed with CH2Cl2 to give pure compound 7g. Pure compound 9 was directly obtained from the reaction mixture by addition of Et2O and washing the solid with the same solvent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | In N,N-dimethyl-formamide; at 130℃; for 0.0833333h;Microwave irradiation; | General procedure: N,N'-Bis-(2-Aminoethyl)-1,3-propanediamine (6) (0.03 mL, 0.17 mmol) and anhydride 5e or h (0.34 mmol) were dissolved in DMF (8 mL). The mixture was stirred under microwave heating (130 C, 450 W) in the presence of a Weflon stirrer for 5 min. The mixture was cooled at room temperature and diluted with a solvent (5e: AcOEt, 15 mL; 5h: Et2O, 15 mL) and brine (10 mL). The organic layer was separated, washed with water, dried over anhydrous Na2SO4 and filtered. Pure compound 7e was obtained after crystallization. Instead, when the ethereal solution was concenterd, a yellow solid was separated corresponding to pure 7h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a 140 ml methanol containing 10 mmol polyamine at -78 C under argon was addeddropwise 10 mmol of trifluoroacetate over 30 min while stirring. Then the stirring wascontinued for another 30 min and Temperature was increased to 0 C to get mostly monoprotection. The remaining amino functional groups were protected by adding excessamount of di-tert-butyl dicarbonate (2 equivalent for each amino group) in methanol over30 to 60 minutes. Then the reaction mixture was continued stirring at room temperaturefor 18 h. Then concentrated aqueous ammonia was added to the above solution till the PH reaches 11. This solution is continued mixing for another 15 h at room temperature.Then methanol is evaporated and the remaining residue was passed through silica columnto get the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In aq. buffer; at 20℃; for 24h;pH Ca. 10;Inert atmosphere; | Streptomycin sulfate (MW 1457.4) and Sodium borohydride were from Sigma. N,N'-Bis(2-aminoethyl)-l,3-propanediamine (APDA) (MW 160.27) was from Kodak. All other reagents and solvents were of the highest available purity and used as purchased. [00129] In a glass crimp cap vial with rubber septum, 500mu of APDA (3 mmole) was dissolved in 3 mL of lOOmM carbonate buffer pH 8.65. 500mg of Streptomycin sulfate (0.34 mmole) was added to APDA solution. pH of the mixture was -10. The reaction was mixed at RT for 24h under argon. ESI of the reaction mixture showed the presence of coupling product (MW = 724) in the solution (m/z 724.5, 362.8). Sodium borohydride (300mg) was added to the reaction and mixed at RT for 48h. ESI of the reaction mixture after reduction with NaBH4 approved the addition of two hydrogen atoms to imine (C=N) bond (m/z 726.6, 363.8). [00130] Purification of APDASTREP was carried out using cationic-HPLC on a PolyCAT A column (4.6x250 mm, from PolyLC Inc.). Acetonitrile (1 mL) was added to 500uL of reaction mixture and vortexed. A biphasic mixture was formed. The upper phase (colorless) was discarded and the lower phase (yellow) containing the product was kept for HPLC. Before running the HPLC, 500 muEpsilon of equilibration buffer (sodium phosphate lOmM pH5.4 containing 55% acetonitrile) was added to the sample and applied to the cationic column. The column was washed (0.7mL/min) with a linear gradient (0 to 0.45 M NaCl in 30 min) using buffer Na-phosphate lOmM pH5.4 containing 1M NaCl and 55% acetonitrile. Fractions collected from anionic-HPLC were analyzed by ESI. The fraction containing the product (27-29.5 min) was concentrated in Speed- Vac. APDASTREP concentrated solution was quantitated in the final solution using Ni titration method. The copper chelate of the product (Cu-EDTAMP) was prepared and used for further studies. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | General procedure: A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with diazacrown derivative 4-9 (0.2-0.25 mmol), Pd(dba)2 (8-16 mol%), BINAP or DavePhos ligand (9-18 mol%), absolute dioxane (10-12 mL), the reaction mixture was stirred for several minutes, then the corresponding polyamine (0.2-0.25 mmol) and NaOt-Bu (0.6-0.75 mmol) were added, and the reaction mixture was stirred at reflux for 24 h. After cooling down to room temperature the residue was filtered off, washed with CH2Cl2 (5-10 mL), the combined organic fractions were evaporated in vacuo, the residue was dissolved in CH2Cl2 (10 mL), washed with distilled water (3 × 10 mL), dried over 4A molecular sieves, and the solvent was evaporated in vacuo. The solid residue was chromatographed on silica gel (40-60 mum) using a sequence of eluents: CH2Cl2, CH2Cl2-MeOH 100:1-3:1, CH2Cl2-MeOH-NH3(aq) 100:20:1-10:4:1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | General procedure: Rifaldehyde (300.0 mg, 0.41 mmol) was dissolved in 30 mL CH2Cl2 and (1,4-bis(3-aminopropyl)-piperazine, N,N-bis(2-aminoethyl)-1,3-propanediamine) (0.2 mmol) in 5 mL of C2H5OH with a catalyst (0.2 mmol ZnCl2 or 0.02 mmol HCl/EtOH) added. The mixtures were stirred at 45 C for half an hour and after that a half of the solvent volume was distilled off. To the cooled reaction mixture (room temperature) the reductant NaBH4 (6.8 mg, 0.18 mmol) was added portionwise over 1 min. The reaction mixture was evaporated to dryness, dissolved in 50 mL of ethyl acetate and extracted twice with 50mL of water and brine. The separated organic layer was evaporated and synthesised derivative (compounds 13-14) was purified by column chromatography with silica gel (25 cm×1 cm, silica gel 60, 0.040-0.063 mm/230-400 mesh ASTM, Fluka) and ethyl acetate/methanol as eluent (from 100:0 to 15:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | General procedure: A two-neck flask equipped with a magnetic stirrer and a reflux condenser was filled with dry argon and then charged with diazacrown ether 3 or 4 (0.2 mmol), Pd(dba)2 (8-16 mol.%), the phosphine ligand BINAP (9-18 mol.%), and anhydrous dioxane (10 mL). After stirring for 2-3 min, an appropriate amine 5 (0.2 mmol) and ButONa (0.6 mmol) were added. The reaction mixture was refluxed for 24 h. After completion of the reaction, the precipitate that formed was filtered off and washed with CH2Cl2 (10 mL). The combined filtrates were concentrated in vacuo. The residue was dissolved in CH2Cl2 (5 mL) and washed with water (3×10 mL). The organic layer was separated, and the aqueous layers were combined to extract organic matter with CH2Cl2 (3×10 mL). The combined organic fractions were dried over 4 A molecular sieves and concentrated in vacuo. The residual thick dark oil was chromatographed on silica gel using the following sequence of eluents: CH2Cl2, CH2Cl2-MeOH (100 : 1)-(3 : 1), CH2Cl2-MeOH-NH3 (100 : 20 : 1)-(10 : 4 : 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | General procedure: A two-neck flask equipped with a magnetic stirrer and a reflux condenser was filled with dry argon and then charged with diazacrown ether 3 or 4 (0.2 mmol), Pd(dba)2 (8-16 mol.%), the phosphine ligand BINAP (9-18 mol.%), and anhydrous dioxane (10 mL). After stirring for 2-3 min, an appropriate amine 5 (0.2 mmol) and ButONa (0.6 mmol) were added. The reaction mixture was refluxed for 24 h. After completion of the reaction, the precipitate that formed was filtered off and washed with CH2Cl2 (10 mL). The combined filtrates were concentrated in vacuo. The residue was dissolved in CH2Cl2 (5 mL) and washed with water (3×10 mL). The organic layer was separated, and the aqueous layers were combined to extract organic matter with CH2Cl2 (3×10 mL). The combined organic fractions were dried over 4 A molecular sieves and concentrated in vacuo. The residual thick dark oil was chromatographed on silica gel using the following sequence of eluents: CH2Cl2, CH2Cl2-MeOH (100 : 1)-(3 : 1), CH2Cl2-MeOH-NH3 (100 : 20 : 1)-(10 : 4 : 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; In 1,4-dioxane; for 24h;Inert atmosphere; Reflux; | 9c was synthesized from compound 5 (136 mg, 0.2 mmol), tetraamine 8c (32 mg, 0.2mmol) in the presence of Pd(dba)2 (9 mg, 8 mol%), BINAP (11 mg, 9 mol%), sodium tert-butoxide (58mg, 0.6 mmol) in 10 mL dioxane. Reflux time 24 h. Eluent CH2Cl2-MeOH-NH3aq 100:20:1, pale-yellowHETEROCYCLES, Vol. 88, No. 2, 2014 1223glassy compound. Yield 27 mg (20%). 1H NMR (CDCl3): 1.49 (bs, 2), 1.97 (bs, 4), 2.46 (t, 3J = 7.0Hz, 4H), 2.64 (bs, 4), 3.05 (t, 3J = 5.2 Hz, 4H), 3.40-3.72 (m, 12), 3.86 (s, 4), 4.03 (bs, 2H), 4.33 (bs,2H), 4.88 (bs, 2), 6.36 (bs, 2), 6.40 (dd, 3J = 7.8 Hz, 4J = 1.9 Hz, 2H), 6.58 (d, 3J = 7.7 Hz, 2H), 6.82(dd, 3J = 9.1 Hz, 4J = 2.4 Hz, 2H), 7.07 (d, 3J = 2.4 Hz, 2H), 7.14 (t, 3J = 7.7 Hz, 2H), 7.34 (d, 3J = 8.8 Hz,2H), two NH protons of dialkylamino groups were not assigned. 13C NMR (CDCl3): 27.4 (22), 30.3(12), 43.1 (22), 47.7 (22), 48.3 (22), 49.0 (22), 53.1 (22), 68.8 (22), 70.9 (22),71.3 (22), 103.0 (2), 109.8 (2), 111.3 (2), 111.5 (2), 115.4 (2), 119.5 (1), 128.2(2), 129.4 (2), 140.3 (1), 142.6 (2), 146.6 (2), 148.6 (2). HRMS (MALDI-TOF) m/z calcdfor C41H57N6O3 [M+H]+ 681.4492, found 681.4464. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane; at 105 - 110℃; for 5h;Inert atmosphere; | Into a 250 mL round bottomed flask was charged 1.6 g bis-aminoethylpropanediamine and 40 mL 1,4-dioxane. To this solution was added 4 g 1,8-naphthalenedicarboxylic acid anhydride. The resulting mixture was heated to 105-110 C (reflux of 1,4-dioxane at 101 C) for 5 h under nitrogen, then allowed to cool to room temperature (RT) overnight. The resulting amber liquid with some dark precipitate was filtered through a Whatman filter and the dark precipitate was washed with dioxane. The dioxane layer was shown to have the desired product by HPLC/MS. The dioxane solution (amber colored) was placed in the refrigerator and overnight the solution solidified (dioxane melting point 12 C). Upon thawing to RT, a beige solid resulted. This solid was collected by filtration and air dried. The recovered solid was dissolved in ca. 60 mL hot toluene (70 C). The hot toluene solution was filtered through a Whatman filter and the toluene filtrate allowed to cool to RT and then at 4 C overnight. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | 2,3,2-tetramine (3.64g, 22.73mmol) was dissolved in 600mL of 62 THF and cooled in an ice bath under argon atmosphere. 63 NaH (600mg, 25.00mmol) was added in small batches and the suspension stirred for 1h at room temperature. 10 3-Iodopropyltrimethoxysilane (6.60g, 22.73mmol) was added and the reaction heated to reflux overnight. THF was removed under vacuum, the residue dissolved in 10mL of 64 CH2Cl2 and filtrated under argon atmosphere. CH2Cl2 was removed under vacuum and the procedure repeated with 5mL of 65 toluene. Evaporation yielded 1 as a slightly yellow viscous liquid (2.29g, 31%). 1H NMR (MeOD): delta=0.54-0.67 (m, 2 H, CH2Si), 1.45-1.75 (m, 4 H, CH2(CH2NH)2, CH2CH2Si), 2.37-2.74 (m, 14 H, CH2NH2, CH2NH), 3.52 (s, OCH3) ppm; 13C NMR (CDCl3): delta=6.70 (CH2Si), 23.21 (CH2CH2Si), 29.83 (CH2(CH2NH)2), 40.93 (CH2NH2), 49.08, 49.67, 50.20, 50.55 (CH2NH), 50.12 (OCH3), 51.84 (CH2CH2CH2Si) ppm; IR: 776 (s), 813 (s), 1074 (s), 1189 (m), 1458 (m), 1593 (w), 2835 (m), 2934 (m), 3254 (w) cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.3% | With triethylamine; In 1,4-dioxane; for 48h;Reflux; Darkness; | To a hot suspension of compound 2 (0.5?g, 1.75?mmol) and triethylamine (0.5?mL) in 1,4-dioxiane (5?mL), N,N-bis(2-aminoethyl)propane-1,3-diamine (140?mg, 0.875?mmol) was added dropwise. The reaction mixture was refluxed for 48?h in dark. The solvent was removed under vacuum. The residue was purified by column chromatography on silica gel eluting with CH3OH/CHCl3 (1/9, v/v). The yellow solid was obtained of 0.445?g, yield of 63.3%. 1H NMR (CDCl3, 400?MHz) delta: 8.57 (d, 2H, J?=?7.2?Hz), 8.54 (d, 2H, J?=?8.0?Hz), 8.42 (d, 2H, J?=?8.4?Hz), 7.72 (m, 2H), 7.23 (d, 2H, J?=?8.0?Hz), 4.28 (m, 4H), 4.02 (m, 8H), 3.25 (m, 8H), 2.960 (m, 4H), 2.757 (m, 4H), 1.86 (s, 2H), 1.69 (m, 2H). 13C NMR (CDCl3, 150?MHz) (ppm): 164.5, 164.0, 155.5, 132.5, 131.2, 130.0, 129.9, 126.1, 125.8, 123.2, 117.1, 114.9, 66.9, 53.4, 47.9, 47.7, 39.7, 30.0. MS (MAIDI-TOF): [M]+ 691.6, calcd for C39H42N6O6, 690.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.8% | With triethylamine; In 1,4-dioxane; for 48h;Reflux; Darkness; | General procedure: To a hot suspension of compound 2 (0.5?g, 1.75?mmol) and triethylamine (0.5?mL) in 1,4-dioxiane (5?mL), N,N-bis(2-aminoethyl)propane-1,3-diamine (140?mg, 0.875?mmol) was added dropwise. The reaction mixture was refluxed for 48?h in dark. The solvent was removed under vacuum. The residue was purified by column chromatography on silica gel eluting with CH3OH/CHCl3 (1/9, v/v). The yellow solid was obtained of 0.445?g, yield of 63.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With hydrogenchloride; In methanol; water; at 20℃; for 36h; | Route A: to a solution of N,N?-bis(aminoethyl)-1,3-propanediamine (100 mg, 0.62 mmol, 3.5 equiv.) in MeOH (3 mL) was added TAB?4HCl (50 mg, 0.18 mmol, 1 equiv.). The mixture was stirred under air at room temperature overnight. The resulting brownish mixture was filtered-off, washed with Et2O, cold EtOH and again Et2O, then dried under vacuum to afford the product as an orange-brown solid (136 mg, 0.47 mmol, 54% yield). Route B: to a solution of QDI[5] (150 mg, 1.10 mmol, 1 equiv.) in MeOH (4 mL) were added 4 mL of a 0.05 M HCl solution in MeOH and N,N?-bis(aminoethyl)-1,3-propanediamine (0.22 mL, 1.32 mmol, 1.2 equiv.). The mixture was stirred at room temperature for 1.5 days. The resulting brownish mixture was filtered-off, washed with Et2O, cold EtOH and again Et2O, then dried under vacuum to afford the product as an orange-brown solid (172 mg, 0.59 mmol, yield 53%). 1H NMR (400 MHz, DMSO-d6, 294 K): delta = 7.65 (br s, 1H), 6.75 (s, 1H), 6.63 (s, 1H), 5.32 (br s, 2H), 5.09 (br s, 2H), 4.16 (t, 3JHH = 5.5 Hz, 2H), 3.67 (t, 3JHH = 5.2 Hz, 2H), 3.58 (t, 3JHH = 5.5 Hz, 2H), 3.41 (t, 3JHH = 5.2 Hz, 2H), 2.25 (quint, 3JHH = 5.5 Hz, 2H). 13C{1H} NMR (100 MHz, DMSO-d6, 294 K): delta = 140.4, 136.5, 135.8, 135.8, 127.6, 119.7, 107.6, 96.7, 48.6, 46.0, 43.8, 36.6, 17.9. HRMS (ESI-TOF): m/z [M]+? for C21H18N7+ calcd. 368.1618, found 368.1614. Elemental analysis for C13H17N6Cl?1 CH3OH?1.5HCl: calcd. C 44.31, H 5.98, N 22.15; found C 44.60, H 6.31, N 22.55%. IR (neat, cm-1): 3410, 3282, 3217, 2113, 2086, 1994, 1634, 1565, 1523, 1448, 1349, 1305, 1286, 1150, 1111, 1062, 870, 746. UV-vis (H2O, 25 C): lambda /nm (epsilon / M-1cm-1) = 415 (7600), 345 (10100), 264 (9730), 233 (23800). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With air; In methanol; at 25℃; | Route A: to a solution of N,N?-bis(aminoethyl)-1,3-propanediamine (100 mg, 0.62 mmol, 3.5 equiv.) in MeOH (3 mL) was added TAB?4HCl (50 mg, 0.18 mmol, 1 equiv.). The mixture was stirred under air at room temperature overnight. The resulting brownish mixture was filtered-off, washed with Et2O, cold EtOH and again Et2O, then dried under vacuum to afford the product as an orange-brown solid (136 mg, 0.47 mmol, 54% yield). Route B: to a solution of QDI[5] (150 mg, 1.10 mmol, 1 equiv.) in MeOH (4 mL) were added 4 mL of a 0.05 M HCl solution in MeOH and N,N?-bis(aminoethyl)-1,3-propanediamine (0.22 mL, 1.32 mmol, 1.2 equiv.). The mixture was stirred at room temperature for 1.5 days. The resulting brownish mixture was filtered-off, washed with Et2O, cold EtOH and again Et2O, then dried under vacuum to afford the product as an orange-brown solid (172 mg, 0.59 mmol, yield 53%). 1H NMR (400 MHz, DMSO-d6, 294 K): delta = 7.65 (br s, 1H), 6.75 (s, 1H), 6.63 (s, 1H), 5.32 (br s, 2H), 5.09 (br s, 2H), 4.16 (t, 3JHH = 5.5 Hz, 2H), 3.67 (t, 3JHH = 5.2 Hz, 2H), 3.58 (t, 3JHH = 5.5 Hz, 2H), 3.41 (t, 3JHH = 5.2 Hz, 2H), 2.25 (quint, 3JHH = 5.5 Hz, 2H). 13C{1H} NMR (100 MHz, DMSO-d6, 294 K): delta = 140.4, 136.5, 135.8, 135.8, 127.6, 119.7, 107.6, 96.7, 48.6, 46.0, 43.8, 36.6, 17.9. HRMS (ESI-TOF): m/z [M]+? for C21H18N7+ calcd. 368.1618, found 368.1614. Elemental analysis for C13H17N6Cl?1 CH3OH?1.5HCl: calcd. C 44.31, H 5.98, N 22.15; found C 44.60, H 6.31, N 22.55%. IR (neat, cm-1): 3410, 3282, 3217, 2113, 2086, 1994, 1634, 1565, 1523, 1448, 1349, 1305, 1286, 1150, 1111, 1062, 870, 746. UV-vis (H2O, 25 C): lambda /nm (epsilon / M-1cm-1) = 415 (7600), 345 (10100), 264 (9730), 233 (23800). |
Tags: 4741-99-5 synthesis path| 4741-99-5 SDS| 4741-99-5 COA| 4741-99-5 purity| 4741-99-5 application| 4741-99-5 NMR| 4741-99-5 COA| 4741-99-5 structure
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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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