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CAS No. : | 5071-96-5 | MDL No. : | MFCD00008115 |
Formula : | C8H11NO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | GRRIMVWABNHKBX-UHFFFAOYSA-N |
M.W : | 137.18 | Pubchem ID : | 21156 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.25 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 40.61 |
TPSA : | 35.25 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -9.88 cm/s |
Log Po/w (iLOGP) : | 1.68 |
Log Po/w (XLOGP3) : | -3.86 |
Log Po/w (WLOGP) : | 1.0 |
Log Po/w (MLOGP) : | 1.21 |
Log Po/w (SILICOS-IT) : | 1.43 |
Consensus Log Po/w : | 0.29 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | 1.43 |
Solubility : | 3690.0 mg/ml ; 26.9 mol/l |
Class : | Highly soluble |
Log S (Ali) : | 3.71 |
Solubility : | 710000.0 mg/ml ; 5180.0 mol/l |
Class : | Highly soluble |
Log S (SILICOS-IT) : | -2.54 |
Solubility : | 0.396 mg/ml ; 0.00288 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | 2735 |
Hazard Statements: | H302-H315-H318-H335 | 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 |
---|---|---|
80% | With potassium carbonate In water; toluene; benzene 1.) 0 deg C, 30 min; 2.) 35 deg C, 24 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With triethylamine In ethanol at 40 - 50℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.08333h; | (5-hydroxyindol-2-yl)-N-[(3-methoxyphenyl)methyl]carboxyamide (5); Dissolved 2.00 g (11.3 mmol) <strong>[21598-06-1]5-hydroxy-2-indolecarboxylic acid</strong>, 1.6 ml (12.4 mmol) 3 methoxybenzylamine, and 5.87 g (11.3 mmol) PyBOP in 10 ml anh. DMF. Cooled to 0 C. and added 5.9 ml (33.9 mmol) DIEA. Stirred for 5 minutes at 0 C. and allowed to warm to room temperature for 1 hour. Recovered 2.83 g (85% yield) TLC Rf=0.34 (1/1 EtOAc/hexanes) 1H NMR (DMSO-d6): 3.70 (s, 3H), 4.43 (d, J=4.4 Hz, 2H) 6.69 (d, J=8.8 Hz, 1H), 6.78 (d, J=7.7 Hz, 1H), 6.83 (s, 1H), 6.86 (s, 1H), 6.94 (s, 1H), 7.20 (m, 3H), 8.92 (t, J=4.4 Hz, 1H), 11.36 (s, 1H) FAB(+) MS m/e 297.3 (M+1) |
85% | With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 1.08333h; | (5-hydroxyindol-2-yl)-N-[(3-methoxyphenyl)methyl]carboxyamide (5) Dissolved 2.00 g (11.3 mmol) <strong>[21598-06-1]5-hydroxy-2-indolecarboxylic acid</strong>, 1.6 ml (12.4 mmol) 3 methoxybenzylamine, and 5.87 g (11.3 mmol) PyBOP in 10 ml anh. DMF. Cooled to 0 C. and added 5.9 ml (33.9 mmol) DIEA. Stirred for 5 min at 0 C. and allowed to warm to room temperature for 1 hour. Recovered 2.83 g (85% yield) TLC Rf=0.34 (1/1 EtOAc/hexanes) 1H NMR (DMSO-d6): 3.70 (s, 3H), 4.43 (d, J=4.4 Hz, 2H) 6.69 (d, J=8.8 Hz, 1H), 6.78 (d, J=7.7 Hz, 1H), 6.83 (s, 1H), 6.86 (s, 1H), 6.94 (s, 1H), 7.20 (m, 3H), 8.92 (t, J=4.4 Hz, 1H), 11.36 (s, 1H) FAB(+) MS m/e 297.3 (M+1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With triethylamine; In butan-1-ol; at 90℃; for 4.0h; | 3 mmol of <strong>[13276-52-3]2,6-dichloropurine riboside</strong> were dissolved in 15 ml of butanol. Subsequently, 4 mmol of 3-methoxybenzylamine and 5 mmol of triethylamine were added and mixture was heated at 90C for 4 hours. After cooling, the precipitated product was filtered off and recrystallised from ethanol. TLC: chloroform-methanol- ammonia (90: 9: 1) single spot. Yield 85 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In DMF (N,N-dimethyl-formamide); water at 20℃; for 24h; | 225 Example 225; N-[3-(methyloxy)phenyl]methyl}-1-oxo-1,2-dihydroisoquinoline-3- carboxamide; A solution of 1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid (105 mg) obtained in Reference Example 99,3- methoxybenzylamine (98 mg), 1-hydroxy-1-H-benzotriazole monohydrate (95 mg) and 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide hydrochloride (130 mg) in DMF (5 mL) was stirred at room temperature for 1 day. 10% Aqueous citric acid solution was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, aqueous sodium hydrogen carbonate and saturated brine, dried and concentrated. The obtained crude crystals were washed with ethyl acetate to give the title compound (39 mg) . melting point: 206-210°C | |
39 mg | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 10 - 35℃; for 24h; | 225 N-[3-(methyloxy)phenyl]methyl}-1-oxo-1,2-dihydroisoquinoline-3-carboxamide Example 225 N-[3-(methyloxy)phenyl]methyl}-1-oxo-1,2-dihydroisoquinoline-3-carboxamide A solution of 1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid (105 mg) obtained in Reference Example 99, 3-methoxybenzylamine (98 mg), 1-hydroxy-1-1-H-benzotriazole monohydrate (95 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (130 mg) in DMF (5 mL) was stirred at room temperature for 1 day. 10% Aqueous citric acid solution was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, aqueous sodium hydrogen carbonate and saturated brine, dried and concentrated. The obtained crude crystals were washed with ethyl acetate to give the title compound (39 mg). melting point: 206-210° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); at 20℃; for 72h; | N-(3-Methoxybenzyl)-5-bromothiophene-3-carboxamide:; 5-Bromothiophene-3-carboxylic acid (70%) (200 mg, 0.6 mmol of mono bromide) was dissolved in DMF with 3-methoxybenzyl amine (0.3 g, 2.2 mmol), EDCI (0.42 g, 2.2 mmol), and HOBt hydrate (0.06g, 0.4 mmol). The reaction mixture was stirred at room temperature for 3 days, diluted with EtOAc and the organic layer washed with 10% citric acid, saturated sodium bicarbonate, and brine. The organic layer was then dried over sodium sulfate and concentrated to an oil, which was purified by column chromatography on silica (10 to 30 5 EtOAc/hexanes) to give the product as a colorless oil, 195 mg, 0.6 mmol, 100%. ¹H NMR 500 MHz (CDC13) 7.81 (1H, s), 7.35 (1H, s), 7.28 (lH, m), 6.93 (lH, m), 6.87 (2H, m), 6.23 (lH, br s), 4.57 (2H, d), 3.84 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 80℃; for 18h; | A solution of commercially available <strong>[6345-43-3]pyrimidine-4,6-dicarboxylic acid dimethyl ester</strong> (1.96 g) and commercially available 3-methoxy-benzylamine (1.38 mL) in dry N,N-dimethylformamide (10 mL) was placed in a preheated oil bath (80 C.). After stirring at this temperature for 18 h the mixture was concentrated and flash filtered (silica, cyclohexane/ethyl acetate). The obtained material was suspended in dry tetrahydrofurane (10 mL) and treated with a solution of lithium hydroxide (642 mg) in water (15 mL). The resulting mixture was stirred at room temperature for 16½ h, diluted with water (35 mL), washed with dichloromethane (3×50 mL) and acidified by addition of a 1M aqueous solution of hydrochloric acid (20 mL). The formed precipitate was isolated by suction, washed with water (2×50 mL) again suspended/dissolved in water (200 mL) and ultrasonificated for 5 min. The remaining precipitate was isolated by suction and dried under reduced pressure to afford the title compound (700 mg; 24%). [MH]+=288. | |
In N,N-dimethyl-formamide; at 80℃; for 18h; | Preparative Example 202; Step A; A solution of commercially available <strong>[6345-43-3]pyrimidine-4,6-dicarboxylic acid dimethyl ester</strong> (1.96 g) and commercially available 3-methoxy-benzylamine (1.38 mL) in dry N,N-dimethylformamide (10 mL) was placed in a preheated oil bath (80 C.). After stirring at this temperature for 18 h the mixture was concentrated and flash filtered (silica, cyclohexane/ethyl acetate). The obtained material was suspended in dry tetrahydrofuran (10 mL) and treated with a solution of lithium hydroxide (642 mg) in water (15 mL). The resulting mixture was stirred at room temperature for 16½ h, diluted with water (35 mL), washed with dichloromethane (3×50 mL) and acidified by addition of a 1M aqueous solution of hydrochloric acid (20 mL). The formed precipitate was isolated by suction, washed with water (2×50 mL) again suspended/dissolved in water (200 mL) and ultrasonificated for 5 min. The remaining precipitate was isolated by suction and dried under reduced pressure to afford the title compound (700 mg; 24%). [MH]+288. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In Petroleum ether; | EXAMPLE 5 2,2-Dimethoxy-N-(3methoxybenzyl)-acetamide 8 g. (58 mmole) 3-methoxybenzylamine and 9 g. (66 mmole) methyl 2,2-dimethoxyacetate are contacted for 48 hours. 70 ml. petroleum ether are then added, the insoluble material is filtered off and the solvent is eliminated. The residual oil is distilled at 145-147 C./0.001 mm.Hg. There are obtained 10 g. of 2,2-dimethoxy-N-(3-methoxybenzyl)-acetamide in the form of a colorless viscous oil. The yield is 72% of theory; B.P. 145-147 C./0.001 mm.Hg. NMR (CDCl3): 7.4- 6.65 (5H, multiplet, Ha); 4.7 (1H, singlet, Hb); 4.4 (2H, doublet, Hc); 3.77 (3H, singlet, Hd, J=6Hz); 3.37 (6H, singlet, He) STR10 Mass spectrum: m/e 239 (M+), 207 (--CH3 OH), 176 (CO), 151, 148, 136 (amine), 121 (tropylium), 91, 75, 47, M* 29.5. Analysis: C12 H17 NO4 (M.W. 239.274): calculated: C 60.23%; H 7.16%; N 5.85%; found: 60.20%; 7.20%; 5.81% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In hexane; ethyl acetate; N,N-dimethyl-formamide; | Compound #12 N-(3-methoxybenzyl)-2-[1,6]naphthyridine-carboxamide To a stirring mixture of 2-[1,6]naphthyridinecarboxylic acid (50 mg, 0.287 mmol) in anhydrous DMF (1.0 mL) at room temperature was added sequentially 1-hydroxybenzotriazole hydrate (42.7 mg, 0.316 mmol), 3-methoxybenzylamine (56.6 muL, 0.431 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarboiimide hydrochloride (61.8 mg, 0.316 mmol). The resulting mixture was allowed to stir at room temperature overnight and it was found to be clear. The solvent was removed under vacuum. Flash column chromatography of the residue (50% hexane/ethyl acetate to 100% ethyl acetate) afforded the desired product as a clear oil (79.1 mg, 94%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; | 53.B; 54.B; 56.B; 57.B; 59.B Step B: To a solution of 3-methoxybenzylamine (7.8 g, 57 mmol) and the acid (7.6 g, 57 mmol) from step A above in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (12.0 g, 62.7 mmol). The reaction solution was stirred at room temperature for 16 hours. The resultant reaction mixture was washed with water, aqueous 1 N hydrochloric acid, water and aqueous saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The crude acetal (13.3 g, 92%) as a light yellow was used in the next step without further purification: 1H NMR (CDCl3, 500 MHz) δ 7.24 (d, J=8.0 Hz, 1H), 6.86 (dd, J=7.5, 0.5 Hz, 1H), 6.83-6.80 (m, 2H), 6.40 (br, 1H), 4.73 (t, J=5.5 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.80 (s, 3H), 3.39 (s, 6H), 2.59 (d, J=5.5 Hz, 2H).; Step B: To a solution of 3-methoxybenzylamine (7.8 g, 57 mmol) and the acid (7.6 g, 57 mmol) from step A above in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (12.0 g, 62.7 mmol). The reaction solution was stirred at room temperature for 16 hours. The resultant reaction mixture was washed with water, aqueous 1 N hydrochloric acid, water and aqueous saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The crude acetal (13.3 g, 92%) as a light yellow was used in the next step without further purification: 1H NMR (CDCl3, 500 MHz) δ 7.24 (d, J=8.0 Hz, 1H), 6.86 (dd, J=7.5, 0.5 Hz, 1H), 6.83-6.80 (m, 2H), 6.40 (br, 1H), 4.73 (t, J=5.5 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.80 (s, 3H), 3.39 (s, 6H), 2.59 (d, J=5.5 Hz, 2H).Step B: To a solution of 3-methoxybenzylamine (7.8 g, 57 mmol) and the acid (7.6 g, 57 mmol) from step A above in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (12.0 g, 62.7 mmol). The reaction solution was stirred at room temperature for 16 hours. The resultant reaction mixture was washed with water, aqueous 1N hydrochloric acid, water and aqueous saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The crude acetal (13.3 g, 92%) as a light yellow was used in the next step without further purification: 1H NMR (CDCl3, 500 MHz) δ 7.24 (d, J=8.0 Hz, 1H), 6.86 (dd, J=7.5, 0.5 Hz, 1H), 6.83-6.80 (m, 2H), 6.40 (br, 1H), 4.73 (t, J=5.5 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.80 (s, 3H), 3.39 (s, 6H), 2.59 (d, J=5.5 Hz, 2H).; Step B: To a solution of 3-methoxybenzylamine (7.8 g, 57 mmol) and the acid (7.6 g, 57 mmol) from step A above in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (12.0 g, 62.7 mmol). The reaction solution was stirred at room temperature for 16 hours. The resultant reaction mixture was washed with water, aqueous 1 N hydrochloric acid, water and aqueous saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The crude acetal (13.3 g, 92%) as a light yellow was used in the next step without further purification: 1H NMR (CDCl3, 500 MHz) δ 7.24 (d, J=8.0 Hz, 1H), 6.86 (dd, J=7.5, 0.5 Hz, 1H), 6.83-6.80 (m, 2H), 6.40 (br, 1H), 4.73 (t, J=5.5 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.80 (s, 3H), 3.39 (s, 6H), 2.59 (d, J=5.5 Hz, 2H).; Step B: To a solution of 3-methoxybenzylamine (7.8 g, 57 mmol) and the acid (7.6 g, 57 mmol) from step A above in dichloromethane (400 mL) at room temperature was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (12.0 g, 62.7 mmol). The reaction solution was stirred at room temperature for 16 hours. The resultant reaction mixture was washed with water, aqueous 1 N hydrochloric acid, water and aqueous saturated sodium bicarbonate, dried over sodium sulfate and concentrated in vacuo. The crude acetal (13.3 g, 92%) as a light yellow was used in the next step without further purification: 1H NMR (CDCl3, 500 MHz) δ 7.24 (d, J=8.0 Hz, 1H), 6.86 (dd, J=7.5, 0.5 Hz, 1H), 6.83-6.80 (m, 2H), 6.40 (br, 1H), 4.73 (t, J=5.5 Hz, 1H), 4.44 (d, J=5.5 Hz, 2H), 3.80 (s, 3H), 3.39 (s, 6H), 2.59 (d, J=5.5 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 20h;Product distribution / selectivity; | Preparation of N-(3-methoxybenzyl)-5-(4, 4, 5, 5-tetramethyl-1 ,3, 2-dioxaborolan-2-yl)-2- thiophenecarboxamide; A mixture of 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-2-thiophenecarboxylic acid (10.1 g, 39.7 mmol), HOBt (6.43 g, 47.6 mmol), and EDC (9.13 g, 47.6 mmol), in DMF (100 ml_) was treated with 3-methoxybenzylamine (5.6 ml_, 43.7 mmol) and stirred at room temperature for 20 hours. The reaction mixture was poured onto ice water (300 mL) and extracted with EtOAc (3 x 150 ml_). The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated to afford the product, N-(3-methoxybenzyl)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxa-borolan-2-yl)-2- thiophenecarboxamide, (12.9 g) as a yellow solid.1 H NMR (400 MHz, DMSO-d6) delta ppm 1.26 (s, 12H), 3.71 (s, 3 H), 4.39 (d, J=6.0 Hz, 2H), 6.78-6.85 (m, 3H), 7.21 (t, J=8.0 Hz, 1 H), 7.51 (d, J=3.7 Hz, 1 H), 7.80 (d, J=3.7 Hz, 1 H), 9.09 (t, J=6.0 Hz, 1 H). | |
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 14h;Product distribution / selectivity; | Synthesis of 2; To a solution of 1 (2.0 g, 12 mmol) in THF (20 mL) and toluene (20 mL) was added pinacol (1.4 g, 12 mmol) and the resulting mixture was concentrated under reduced pressure to dryness. The solids obtained was dissolved in THF (20 mL) and toluene(20 mL) and concentrated under reduced pressure two more times. The intermediate solid was dissolved in DMF (40 mL) followed by the addition of EDC (2.3 g, 12 mmol),HOBt (1.6 g, 12 mmol), DIPEA (4.2 mL, 24 mmol) and amine (1.6 g, 12 mmol). The resulting reaction mixture was stirred for 14 h. The reaction mixture was diluted withH2O (50 mL) and ethyl acetate (100 mL). The layers were separated and the organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (silica gel, 0-50% ethyl acetate/heptane) to obtain 2 as a pale yellow solid (0.37 g, 8.4% for two steps): 1H NMR (500 MHz, DMSO-c/6) delta 9.10 (t, J = 6.0 Hz, 1 H), 7.84 (d, J = 4.0 Hz, 1 H), 7.54 (d, J = 4.0 Hz, 1 H), 7.24 (t, J = 8.0 Hz,1H), 6.88-6.80 (m, 3H), 4.42 (d, J = 6.0 Hz, 2H)1 3.73 (s, 3H), 1.29 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A library of compounds in which R4 was various groups having the formula [CONHR »] was prepared by the process described above using 4-fluoro-3-nitrobenzoic acid, as follows: [72] Aldehyde resin was mixed with a primary amine (R17-NH2) in [DICHLOROETHANE] (DCE), triethylorthoformate (TEOF), and DMF (containing [1%] acetic acid) in a 1: 1: 1 ratio. After shaken overnight, sodium triacetoxyborohydride (20 eq. ) dissolved in DMF was added (Abdel-Magid, A. F. , et al., Tetrahedron Lett, 3 1: 5595-5598 (1990) ). After the mixture was shaken at room temperature overnight, the resin was filtered and washed with DMF (3 x 5 mL), [MEOH] [(3 X 5] mL), DMF [(3 X 5] mL), [MEOH] [(3 X 5] mL), and [CH2CL2] [(3 X 5] mL). The resin was washed twice with 5 mL DMF containing [1%] Hunig's base. To the filtered resin was added a mixture of 4-fluoro-3-nitrobenzoic acid (FNBA, 10 eq. ) and diisopropylcarbodiimide (DIC, 5 eq. ) in 2: 1 DMF : DCM. After shaking at room temperature overnight, the resin was filtered and washed with DMF (3 x 5 mL) and [CH2C12] (3 x 5 mL). [73] The resin was shaken with a primary amine [(R2-NH2)] in DMF for 8 hrs, filtered, and washed with DMF (6 x 5 mL), [MEOH] [(3 X 5] mL), and CH2C12 (3 x 5 mL). The aryl nitro group was reduced by the addition of tin (II) chloride dihydrate (20 eq. , >2 M) and N-methyl morpholine (NMM, 20 eq. ) in N-methyl pyrrolidinone (NMP). After shaken at room temperature overnight, the resin was filtered and washed with NMP (3 x 5 mL), [MEOH] (3 x 5 mL), and [CH2CI2 (3 X 5] mL). The resulting resin was shaken at room temperature with cyanogen bromide (5 eq. ) overnight, filtered, and washed with CH2Cl2 (3 x 5 mL), [MEOH] (3 x 5 mL), and CH2CI2 (3 x 5 mL). To produce a free amine, the resin was shaken for 30 min. in CHCl2 with the addition of sodium methoxide in methanol, filtered, and washed with CH2Cl2 [(4 X 5] mL). [[74]] In the final diversification step, the resin was heated at 500 C in DMF with a mono- substituted epoxide [[RLCH (-CH2O-)].] After shaking for 2 to 4 days the resin was filtered and washed with DMF (5 x 5 mL), [MEOH] [(3 X 5] mL), and CH2Cl2 (3 x 5 mL). T he resin-bound benzimidazole was cleaved from the solid-support by treatment with TFA: [CH2C12] (2: 3) for 1 hour at room temperature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃;Reflux; | Production example 79 A mixture of 0.17 g of 3-methoxybenzylamine, 0.15 g of <strong>[846021-26-9]2-amino-6-methylnicotinic acid</strong>, 0.15 g of 1-hydroxybenzotriazole, 0.25 g of WSC, 0.35 g of pyridine and 2 ml of DMF was stirred under heating to reflux for 30 minutes, and then at a room temperature for 1 day. Thereafter, water was added to the reaction mixture, and the precipitated solid was then collected by filtration. The obtained solid was subjected to silica gel column chromatography, so as to obtain 0.22 g of N-(3-methoxyphenyl)methyl-<strong>[846021-26-9]2-amino-6-methylnicotinic acid</strong> amide (hereinafter referred to as the present compound 95).The present compound 95 [Show Image] 1H-NMR (CDCl3) delta: 2.38 (3H, s), 3.81 (3H, s), 4.56 (2H, d, J = 5.6 Hz), 6.23 (1H, br s), 6.39 (2H,br s), 6.44 (1H, d, J = 8.0 Hz), 6.82-6.94 (3H, m), 7.24-7.30 (1H, m), 7.49 (1H, d, J = 8.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; | A solution of 6-bromo-lH-indole-2-carboxylic acid (1.0 equiv), a primary or secondary amine (1.0 equiv) and Et3N (2.0 equiv) was prepared in anhydrous DMF at room temperature. To this solution was then added HATU (1.3 equiv). The solution was then stirred until the reaction was complete by LC/MS (-1-2 h). Upon completion, the solution was diluted with EtOAc and washed with H20. The aqueous portion was extracted with additional EtOAc and the combined organic portions were dried over MgS04. Purification on Si02 (Hexane/EtOAc or CH2Cl2/MeOH+NH4OH) gave the intermediate carboxamides. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 2h; | A solution of the carboxcylic acid (1.0 equiv), a primary or secondary amine (1.0 equiv) and Et3N (2.0 equiv) was prepared in anhydrous DMF at room temperature. To this solution was then added HATU (1.3 equiv). The solution was then stirred until the reaction was complete by LC/MS (-1-2 h). Upon completion, the solution was diluted with CH2C12 and washed with saturated NH4C1 solution. The aqueous portion was extracted with additional CH2C12 and the combined organic portions were dried over MgS04. Purification on Si02 (Hex/EtOAc) gave the desired carboxamides |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU In N,N-dimethyl-formamide at 20℃; | ||
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane | 2.e Synthesis of 6-chloro-N-(3-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (6b) Solution of compound 5 (100mg, 0.51mmol) was dissolved in 5mL of dichloromethane, was added HATU (293mg, 0.77 mmol), followed by the slow addition of triethylamine (155mg, 1.53mmol), 3-methoxy benzylamine and stirred overnight, then saturated Aqueous ammonium chloride solution and extracted with dichloromethane (10 ml x 2), organic phases were combined and concentrated to column chromatography to give the title compound 6b |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With manganese(IV) oxide; oxygen; In dichloromethane; at 180℃; under 15001.5 Torr; for 24h; | Add 300mg of manganese dioxide, 60mg of 3-methoxybenzylamine in 6g of dichloromethane (the mass in the mixture is thick)Degree: 1.0%), uniformly mixed; charged with 2MPa oxygen, reacted at 180 C for 24 hours, 3-methoxybenzylamine conversion rate of 98.6%, correspondingThe selectivity to 3-methoxybenzamide was 99.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyridine; In dichloromethane; at 20℃; | General procedure: A mixture of 3- or 4-cyanobenzenesulfonyl chloride (605 mg, 3 mmol), the amine (3.3 mmol) and pyridine (736 mg, 9.3 mmol) was stirred overnight at room temperature in abs dichloromethane (40 mL). After removal of the solvent at reduced pressure, nitriles B were obtained by flash column chromatography (dichloromethane) and recrystallisation from ethyl acetate/hexane or toluene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | Stage #1: 3-METHOXYBENZYLAMINE; 4-chloro-3-nitro-5-sulfamoylbenzoic acid In water at 20℃; for 15h; Stage #2: With hydrogenchloride In water Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 2h; | A solution of 6-bromo-indazole-3-carboxylic acid (1.0 equiv), an amine(1.0 equiv) and Et3N (2.0 equiv) was prepared in anhydrous DMF at room temperature. To this solution was then added HATU (1.3 equiv). The solution was then stirred until the reaction was complete by LC/MS (-1-2 h). Upon completion, the solution was diluted with EtOAc and washed with H20. The aqueous portion was extracted with additional EtOAc and the combined organic portions were dried over MgS04. Purification on S1O2 (Hexane/EtOAc) gave the intermediate bromo-indazole carboxamide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With HATU; In N,N-dimethyl-formamide; at 20℃; | To a solution of 6-bromoimidazo[l,2-a]pyridine-2-carboxylic acid (100 mg, 0.41 mmol) in DMF (0.5 mL) was added 3-methoxybenzylamine (75 mg, 0.55 mmol) and HATU (190 mg, 0.50 mmol). The resulting mixture was stirred at room temperature overnight. After removal of solvent by rotary evaporation, the residue was dissolved in ethyl acetate (15 mL) and washed with a saturated aqueous Na2C03 solution (2 x 10 mL), and brine (10 mL), dried over Na2S04, and filtered. The solvent was removed in vacuo and the crude amide product was purified by flash column chromatography (10-65% ethyl acetate in hexanes) to afford the title compound (119 mg, 79%). LC-MS: single peak at 254 nm, MH+ calcd. for C16H15BrN302: 360, obtained: 360. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With HATU; In N,N-dimethyl-formamide; at 20℃; | To a solution of 6-bromoimidazo[l,2-a]pyridine-3-carboxylic acid (50 mg, 0.21 mmol) in DMF (0.5 mL) was added 3-methoxybenzylamine (37 mg, 0.27 mmol) and HATU (95 mg, 0.25 mmol). The resulting mixture was stirred at room temperature overnight. After removal of solvent by rotary evaporation, the residue was dissolved in ethyl acetate (15 mL) and washed with a saturated aqueous Na2C03 solution (2 x 10 mL), and brine (10 mL), dried over Na2S04, and filtered. The solvent was removed in vacuo and the crude amide product was purified by flash chromatography on silica gel to afford the title compound (52 mg, 70%). LC-MS: single peak at 254 nm, MH+ calcd. for C16H15BrN302: 360, obtained: 360. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 17h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.4% | In 1L with thermometer, dropping funnel, adjustable power heating jacket, 708.0 g (3.5 mol) of 40% hydrobromic acid was put into the reactor of the agitator and distillation device, 137.2 g (1.0 mol) of 3-methoxybenzylamine was slowly added dropwise with a dropping funnel while stirring with a stirrer, Drop by drop, Raise the excess water to remove excess water until the distillation temperature reaches above 120C (in this case, the temperature in the reactor reaches above 126C ), Reduce the heating rate, make it into a reflux state or distill at a very slow rate, Keep the temperature in the reactor above 126C , The generated gas is absorbed by solvent or recovered by freezing method to protect the environment, When no more gas is observed, increase the heating rate again and continue the distillation. Recover excess hydrobromic acid until the temperature in the reactor reaches above 132C , slightly colder, Add 0 ml of water, dropwise add a pre-cooled 30% mass concentration sodium hydroxide aqueous solution under water cooling, Make a precipitate, drop again, until the precipitate completely disappears, extract and wash twice with 50 ml of benzene, The organic phase recovers benzene, the water phase is adjusted with 36.5% hydrochloric acid under ice-cooling to adjust the pH: 9-10, stir to crystallize, Filtration with suction, the filter cake was washed with 250 ml of water, then dried with vacuum, dried in vacuum, That is, the absolute pressure is less than 10 mm Hg, after rotating and drying at room temperature for 2 hours, Then increase it to 80 according to the heating rate of 10 / hour, and bake it to constant weight to get the finished product. Total: 119.3 g, water content determined by Karl Fischer method: 1.53%, molar yield: 95.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: linoleic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: 3-METHOXYBENZYLAMINE With dmap In dichloromethane at 20℃; for 18h; | 4.1.1. N-benzylpalmitamide (3a) General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1′-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153μL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87° [lit.45 mp 94.5-95°, and46 fp 95.1°]; 1H NMR (400MHz, CDCl3) δ 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); 13C NMR (CDCl3, 100MHz) δ 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346. |
39% | Stage #1: linoleic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.25h; Inert atmosphere; Stage #2: 3-METHOXYBENZYLAMINE In dichloromethane Inert atmosphere; | |
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 40℃; for 0.5h; | 5 A one-step chemical synthesis of maca amide-N-(m-methoxybenzyl)-9Ζ,12Z-octadecadienamide 0.02 mol of HOAt, 0.02 mol of EDC · HCl and 0.02 mol of DIPEA were weighed in 30 mL of DCM and 0.01 mol of benzylamine, 0.01 mol of linoleic acid was added and stirred at 40 ° C for 30 min. 50 mL of ion water, stirred at room temperature for 30 min, evaporated to dryness, extracted with chloroform, extracted with nitrogen to the volume without reducing the product.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | Stage #1: 7-phenylheptanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: 3-METHOXYBENZYLAMINE With dmap In dichloromethane at 20℃; for 18h; | 4.1.21 N-(3-Methoxybenzyl)-7-phenylheptanamide (13a) General procedure: To a solution of 7-phenylheptanoic acid (500mg, 2.42mmol) in dichloromethane ((10mL) was added 1.1′-carbonyldiimdazole (432mg, 2.67mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of 3-methoxybenzylamine (372μL, 2.91mmol) and 4-dimethylaminopyridine (30mg, 0.24mmol) in dichloromethane (5mL). The reaction was carried out at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over sodium sulfate and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (457mg, 58%, mp 68-70°); 1H NMR (400MHz, CDCl3) δ 7.22-7.28 (m, 3 H), 7.15-7.18 (m, 3H), 6.85 (d, J=7.2Hz, 1H), 6.80-6.82 (m, 2H), 5.69 (br s, 1H), 4.41 (d, J=6.0Hz, 2H), 3.79 (s, 3H), 2.59 (t, J=7.6Hz, 2H), 2.20 (t, J=7.6, 2H), 1.59-1.68 (m, 4H), 1.33-1.37 (m, 4H); 13C NMR (CDCl3, 100MHz) δ 173.08, 160.11, 142.92, 140.21, 129.99, 128.63, 128.47, 125.85, 120.26, 113.63, 113.16, 55.47, 43.77, 36.98, 36.09, 31.52, 29.38, 29.18, 25.91; LCMS, C21H27NO2, [M+H]: 326. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | Stage #1: 6-phenylhexanic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: 3-METHOXYBENZYLAMINE With dmap In dichloromethane at 20℃; for 18h; | 4.1.21 N-(3-Methoxybenzyl)-7-phenylheptanamide (13a) General procedure: To a solution of 7-phenylheptanoic acid (500mg, 2.42mmol) in dichloromethane ((10mL) was added 1.1′-carbonyldiimdazole (432mg, 2.67mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of 3-methoxybenzylamine (372μL, 2.91mmol) and 4-dimethylaminopyridine (30mg, 0.24mmol) in dichloromethane (5mL). The reaction was carried out at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over sodium sulfate and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (457mg, 58%, mp 68-70°); 1H NMR (400MHz, CDCl3) δ 7.22-7.28 (m, 3 H), 7.15-7.18 (m, 3H), 6.85 (d, J=7.2Hz, 1H), 6.80-6.82 (m, 2H), 5.69 (br s, 1H), 4.41 (d, J=6.0Hz, 2H), 3.79 (s, 3H), 2.59 (t, J=7.6Hz, 2H), 2.20 (t, J=7.6, 2H), 1.59-1.68 (m, 4H), 1.33-1.37 (m, 4H); 13C NMR (CDCl3, 100MHz) δ 173.08, 160.11, 142.92, 140.21, 129.99, 128.63, 128.47, 125.85, 120.26, 113.63, 113.16, 55.47, 43.77, 36.98, 36.09, 31.52, 29.38, 29.18, 25.91; LCMS, C21H27NO2, [M+H]: 326. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1?-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153muL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87 [lit.45 mp 94.5-95, and46 fp 95.1]; 1H NMR (400MHz, CDCl3) delta 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); 13C NMR (CDCl3, 100MHz) delta 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346. | |
With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; | 0.02 mol of HOAt, 0.02 mol of EDC · HCl and 0.02 mol of DIPEA were weighed in 30 mL of DCM and 0.01 mol of m-methoxybenzylamine, 0.01 mol of linolenic acid was added and stirred overnight at room temperature; 50 mL of deionized water was added, Stirring for 30min, adding chloroform extraction, extraction layer nitrogen blowing to the volume is no longer reduced products |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: n-tetradecanoic acid With 1,1'-carbonyldiimidazole In dichloromethane at 20℃; for 2h; Stage #2: 3-METHOXYBENZYLAMINE With dmap In dichloromethane at 20℃; for 18h; | 4.1.1. N-benzylpalmitamide (3a) General procedure: To a solution of palmitic acid (300mg, 1.17mmol) in dichloromethane (DCM, 10mL) was added 1,1′-carbonyldiimdazole (209mg, 1.29mmol). The reaction was stirred at room temperature for 2h. The reaction mixture was slowly added to a solution of benzylamine (153μL, 1.40mmol) and 4-dimethylaminopyridine (14mg, 0.12mmol) in dichloromethane (5mL). The solution was stirred at room temperature for 18h. DCM (100mL) and saturated aqueous NaHCO3 (30mL) were added to the reaction mixture. The organic layer was separated and washed with H2O (30mL), brine (30mL), dried over anhyd sodium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude was purified by flash chromatography on silica gel eluting with hexane/EtOAc (3:1, v/v) to give the title compound as a white solid (578mg, 86%). Mp 85-87° [lit.45 mp 94.5-95°, and46 fp 95.1°]; 1H NMR (400MHz, CDCl3) δ 7.32-7.36 (m, 2H), 7.26-7.30 (m, 3H), 5.72 (br s, 1H), 4.45 (d, J=6.0Hz, 2H), 2.21 (t, J=7.2Hz, 2H), 1.61-1.67 (m, 2H), 1.25-1.34 (m, 24H), 0.88 (t, J=6.8Hz, 3H); 13C NMR (CDCl3, 100MHz) δ 173.21, 138.66, 128.92, 128.05, 127.71, 43.80, 37.06, 32.16, 29.92, 29.89, 29.84, 29.73, 29.59, 29.56, 26.01, 22.93, 14.36; LCMS, C23H39NO, [M+H]: 346. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 10h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 10 h / 20 °C 2: trifluoroacetic acid; sodium nitrite / dichloromethane / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; at 20℃; for 1h;Inert atmosphere; | 58A: 4-bromo-N-(3-methoxybenzyl)-3-methylbenzamide [0270] To a solution of <strong>[7697-28-1]4-bromo-3-methylbenzoic acid</strong> (100 mg, 0.465 mmol) in DCM (2 mL) were added (3-methoxyphenyl)methanamine (70.2 mg, 0.512 mmol), DIEA (0.244 mL, 1.395 mmol) and HATU (212 mg, 0.558 mmol) at RT. The reaction was stirred under argon at RT for 1 h. The crude product was purified by normal phase chromatography. 58A was obtained as white solid (155 mg, 0.464 mmol, 100% yield). LCMS (ESI) m/z: 336.0 (M+H)+; 1H NMR (400 MHz, CHLOROFORM-d) delta 7.67 (d, J=2.2 Hz, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.46-7.39 (m, 1H), 7.30-7.24 (m, 1H), 6.92 (dd, J=7.6, 0.6 Hz, 1H), 6.88 (t, J=1.8 Hz, 1H), 6.84 (dt, J=8.1, 1.3 Hz, 1H), 6.38 (br. s., 1H), 4.60 (d, J=5.7 Hz, 2H), 3.80 (s, 3H), 2.43 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | In N,N-dimethyl-formamide; at 80 - 90℃; for 5.0h; | General procedure: A mixture of compound 6a (240 mg, 4.00 mmol) and 3-methoxybenzylamine (138 mg, 1.00 mmol) in DMF (3 mL) washeated at 90 C for 5 h. The reaction mixture was concentratedunder reduced pressure. The residue was diluted with ethyl acetate,washed with brine, dried over anhydrous Na2SO4 and concentratedunder reduced pressure. The crude product was purified bypreparative HPLC and crystallized from ethanol-diethyl ether togive 7a as a beige powder (88.5 mg, 42%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72.4% | With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine; In N,N-dimethyl-formamide; for 4 - 10h;Reflux; Inert atmosphere; | A solution of acid 4 (0.09 g, 0.47 mmol) in dry DMF (2 mL) treated sequentially with amine (5a-i, 6a-e and 7a-h; 0.517 mmol)and triethylamine (0.94 mmol) was stirred under a N2 atmosphere for 15 min, later TBTU (0.56 mmol) was added and reaction mixture refluxed for 4-10 h. The reaction mixture was quenched with aq satd NH4Cl solution (10 mL). After 10 min, it was diluted withCHCl3 (2 10 mL) and washed with water (10 mL), NaHCO3 solution(10 mL) and brine (10 mL). The organic layers were dried over anhydrous sodium sulfate, evaporated and the residue purified by column chromatography using 30% ethyl acetate in pet. ether to afford corresponding amides 8a-i, 9a-e and 10a-h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In water; at 80℃; for 0.283333h;Microwave irradiation; | General procedure: To a reaction vial, a suspension of <strong>[132521-66-5]2,4-dichloro-3-nitroquinoline</strong>(243 mg, 1 mmol) in water (1 mL) was added benzyl amine (0.11mL,1 equiv.) and the mixture was heated under microwave irradiation using Biotage initiator for 10 min at 80 C. After the completion of the reaction (TLC), water was removed from mixture, dried and purified through column chromatography to afford 1a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 16h; | General procedure: To solutions of <strong>[120-36-5]2-(2,4-dichlorophenoxy)propanoic acid</strong> (100 mg,0.43 mmol) in DMF (2 mL) were added 2-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate (HATU; 200 mg,0.53 mmol), the corresponding benzylamines (0.50 mmol), anddiisopropylethylamine (100 lL, 0.57 mmol). The resulting mixtureswere stirred at room temperature for 16 h, then poured intowater (20 mL). The aqueous mixtures were then stirred at roomtemperature until solids precipitate. The solids were filtered,rinsed with water, and dried to provide solids that were recrystallizedfrom CH2Cl2/hexane to provide the products 34a-y. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 16h;Inert atmosphere; | [000210] To a stirred solution of 6 (50 mg, 0.18 mmol) in DMF (3 mL) under argon atmosphere were added EDCI.HC1 (50 mg, 0.22 mmol), HOBt (35 mg, 0.22 mmol), 2-(5-methyl- 1, 3, 4-thiadiazol-2-yl) ethan-1-amine hydrochloride 187 (50 mg, 0.22 mmol) and diisopropyl ethyl amine (0.1 mL, 0.55 mmol) at 0 C; warmed to RT and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and stirred for 1 h. The crude was extracted with EtOAc or the precipitated material was either directly dried in vacuo or triturated or purified through silica gel column chromatography to afford the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | In 1,4-dioxane; at 20℃; | General procedure: To a solution of compound 4 (2.43 g, 0.01 mol) in 25 mL dioxane was added 1-(2,6-Dichloro-3-fluorophenyl)ethan-1-amine (3.12 g, 0.015 mol), and then the reaction mixture was stirred at room temperature overnight. After that, the mixture was poured into 150 mL H2O, and then the resulting precipitate was filtered, washed with 50% ethanol, and dried overnight under vacuum to give 5a as white solid (3.58 g, yield, 86%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With copper-based metal-organic framework-74 | |
61% | Stage #1: phenyl(pyridin-2-yl)methanone With manganese(IV) oxide; toluene-4-sulfonic acid at 20℃; for 0.25h; Inert atmosphere; Stage #2: 3-METHOXYBENZYLAMINE at 170℃; for 5.5h; Inert atmosphere; Microwave irradiation; | General procedures for the preparation of imidazo[1,5-a]pyridine and-quinoline derivates General procedure: Ketone (1.1 mmol), activated MnO2 (1.8 mmol), and pTsOH (0.3 mmol) were stirred briefly in a 15 mL round bottom flask at room temperature for 5 min. Afterward, the mixture was heated in an open microwave reactor (equipped with a condenser) for 5.5 h at 170 °C (max. 300 W). During this time, the amine (1.6 mmol) was added with a syringe pump (PTFE tube). The crude product was purified via flash chromatography or recrystallization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 - 60℃; for 22h; | EXAMPLE 9: Synthesis of 6-(3-methoxybenzylamino)-9- -D-2'-deoxyribofuranosylpurine <strong>[890-38-0]2'-deoxyinosine</strong> (252 mg) and BOP (531 mg) were dissolved in dry DMF (5 ml) and stirred at laboratory temperature under argon atmosphere. After five minutes, DIPEA (261 mu) and 3- methoxybenzylamine (167 mu) were added. Reaction mixture was stirred at laboratory temperature for 16 hrs. Reaction process was controlled via TLC (mobile phase: chloroform-methanol-25% aqueous ammonia, 4 : 1 : 0.05). As soon as the conversion was not complete, next portion BOP (354 mg; 0.8 mmol) was added and reaction mixture was heated to 60 C and stirred for 6 hrs. As soon as there were not detected a spot of starting <strong>[890-38-0]2'-deoxyinosine</strong>, reaction mixture was evaporated using vacuum evaporator (maximal temperature 55 C). A residue (cca 1.5 g ) was chromatographically purified using silica gel (150 g); mobile phase: 0-20 % methanol in dichlormethane. Yield: 270 mg (79 %), HPLC-MS purity: 98+%, [M+H+] 372, mp 165-170 C, C/H/N: 58,2/58,1 ; 5,7/5,7; 18,9/18,8; lR(OMSO-d6, 300 MHz) delta ppm: 2.25-2.37 (m, 1H), 2.45- 2.64 (m, 1H), 3.50-3.68 (m, 2H), 3.70 (s, 3H), 3.85-3.90 (m, 1H), 4.33-4.45(m, 1H), 4.67 (bs, 2H), 4.85 (t, 1H), 5.10 (d, / = 4.0 Hz), 6.30 (t, / = 6.9 Hz), 6.77 (d, / = 7.1 Hz), 6.89 (s, 1H), 6.91 (s, 1H), 7.20 (t, / = 7.6 Hz), 8.19 (s, 1H), 8.21 (s, 1H), 8.34 (bs, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 24h;Inert atmosphere; | General procedure: To a stirred solution of corresponding amine (1.0 or 2.0 equiv) in CH2Cl2 (0.2 M) were added at 0C DCC (1.3 equiv), DMAP (0.13 equiv) and 3-butenoic acid (1.3 equiv). The reaction mixture was stirred for 10 minutes at 0 C, then for 24 hours at room temperature. The precipitate was filtered off and washed with CH2Cl2 (25 mL). The organic layer was hydrolyzed with saturated aqueous NaHCO3, extracted and dried over MgSO4 and concentrated at reduced pressure. The crude product was purified by silica gel column chromatography to afford the corresponding allyl-amide 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tert.-butylhydroperoxide at 120℃; for 5h; Ionic liquid; | |
79% | With tert.-butylhydroperoxide; sodium chloride; sodium hydroxide In water monomer at 90℃; for 8h; Green chemistry; | General procedure for the synthesis of 4-methoxy benzoicacid from 4-methoxy benzylamines General procedure: A 50 mL of round bottom flask was charged with a magneticbead,0.1 g (0.729 mmol) of 4- methoxy benzyl amine, 0.0084 g ofNaCl (20 mol%), 0.116 g of NaOH (4 equiv) and 0.336 g of aq. TBHP (5equiv) in 0.3 mL of deionised H2O and it was heated at 90 C for 8 h. Afterwards, the reaction mixture was neutralized by aq. HCl and extracted with EtOAc. The organic layer was dried over anhydrousNa2SO4 and after evaporation of the solvent, the crude mixture waspurified by the silica gel column chromatography with EtOAc:Hexane (06:94 v/v) as eluent. 4-methoxy benzoic acid was obtainedin 84% yield (93 mg). |
Multi-step reaction with 2 steps 1: 4-phenylnaphthalene-1,2-dione; N,N,N-tributyl-1-butanaminium iodide / acetonitrile; water monomer / 24 h / 80 °C 2: tert.-butylhydroperoxide / water monomer / 24 h / 80 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; for 24h; | General procedure: Into a clear solution of 2-(Boc-amino)benzaldehyde 1 (1 mmol) in methanol (5 mL) was added amine 2 (1 mmol) and stirred for 5 minutes at room temperature. Carboxylic acid 3 (1 mmol) and methyl isocyanide (4,1 mmol) were then added simultaneously. The mixture was stirred until no noticeable amounts of starting material were visible by TLC. Upon completion of the reaction, methanol was evaporated under reduced pressure and the crude Ugi products, without any purification, dissolved in a CH2Cl2 and trifluoroaceticacid mixture (1:1, 2 mL) and subsequently stirred at room temperature for 5 h. The reaction progress was monitored by TLC and upon completion of the reaction the solvent was evaporated under reduced pressure. Without any purification, the crude compound was dissolved in acetonitrile (2 mL) and K2CO3 (2 mmol) was added. The reaction was allowed to stirunder refluxing conditions for 1 h and the reaction was monitored for completion using TLC. Upon noted completion of the reaction, the mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The crude compound(s) was subjected to flash column chromatography (EtOAc/hexanes) to yield pure compounds 7a-k. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 40℃; for 16h; | After adding 3-methoxybenzylamine (38 muL, 1.2 eq.), EDC-HCl (72 mg, 1.5 eq.), DMAP (1.5 mg, 0.05 eq.) and Et3N (70 muL, 2 eq.) to a solution of 2-(4-chloro-2-methylphenoxy)acetic acid (50 mg, 0.25 mmol) in CH2Cl2 (1 mL) at 0 C. and stirring at 40 C. for 16 hours, the reaction mixture was diluted with CH2Cl2 (2 mL) and washed with 15% HCl (1 mL). The aqueous layer was extracted once more with CH2Cl2 (2 mL) and the organic layer was dried with MgSO4 and concentrated under reduced pressure. The obtained crude residue was purified by silica gel column chromatography (hexane:ethylacetate:dichloroethane=20:1:2 to 10:1:2, volume ratio), affording a [Chemical Formula 16] compound as a white solid. (0141) White solid, mp: 95.8-96.5 C.; 1H NMR (400 MHz, CDCl3) delta 7.26 (t, J=7.8 Hz, 1H), 7.16-7.10 (m, 2H), 6.88-6.78 (m, 4H), 6.70 (d, J=8.4 Hz, 1H), 4.55-4.51 (m, 4H), 3.78 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz, CDCl3) delta 168.1, 160.1, 154.1, 139.3, 131.0, 130.0, 128.5, 126.9, 119.8, 113.2, 113.2, 112.8, 68.0, 55.4, 43.1, 16.4; HRMS (ESI-QTOF) m/z [M+H]+ calcd for C17H17ClNO3 320.1048. found 320.1043. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With triethylamine In tetrahydrofuran at 20℃; | 3.2. General Procedure for Synthesis of Intermediate 5a-e General procedure: Compounds were prepared according to methods describedby us [23] and others [17, 26]. A solution of 2,4-dichloroquinazoline 1.0 equiv in THF, alkylamine 1.0 equivand triethylamine 1.2 equiv were added. The reaction proceeded at room temperature until the reaction was finished as observed by TLC. The mixture was concentrated in vacuo,redissolved in ethyl acetate and washed with saturated Na-HCO3 and extract. The organic layer was collected, dried by anhydrous Na2SO4, filtered, and dried under reduced pressure to give the compound as a solid. |
With triethylamine In tetrahydrofuran at 20℃; | General procedure for synthesis of compounds 1-10 General procedure: A solution of 2,4-dichloroquinazoline (1.0 equiv.) in THF, triethylamine (1.2 equiv.) and alkylamine (1.2 equiv.) were added. The reaction stirred at room temperature until cannot see reactant spots on TLC. The solvent was removed by evaporated under reduced pressure, dissolved in ethyl acetate and washed with saturated sodium chloride and extracted. The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and dried under vacuum to give the compound as a solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With palladium diacetate; potassium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 130℃; for 18h;Inert atmosphere; | General procedure: Solid starting materials were placed in a 100 cm3 3-necked flask, evacuated, and flushed with argon three times. Then, the liquid starting materials and, finally, toluene were added through the septum with a syringe. The mixture was heated at 130 °C (oil bath temperature) maintaining the argon atmosphere with a balloon. The reaction was stopped after 18 h (TLC). After cooling to r.t., the solid material was removed by filtration and washed with CH2Cl2.The combined organic layers were evaporated and the resulting crude product was purified by flash column chromatography (LP/EtOAc) starting with 5percent EtOAc to 10percent EtOAc over the course of 20 min. Then, flash column chromatography was continued with 10percent EtOAc. Drying under reduced pressure delivered the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | Stage #1: 2-[2-(pyridin-3-yl)-1,3-thiazol-4-yl]acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.5h; Stage #2: 3-METHOXYBENZYLAMINE In dichloromethane at 0 - 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With sodium carbonate In N,N-dimethyl-formamide at 130℃; | 5.1.4. Nucleophilic substitution of dichlorophthalazine 12a withbenzylamine and phenethylamine derivatives: general method C forthe preparation of compounds 14a-g and 15a-d General procedure: A mixture of 2,6-dichlorophthalazine 12a (1.0 equiv.), theappropriate benzylamine or phenethylamine derivative (1.1 equiv.)and Na2CO3 (2.0 equiv.) in DMF (0.3 mmol/mL) was heated overnightat 130 °C. After cooling, the reaction media was diluted withwater and the aqueous phase was extracted 3 times with EtOAc.The organic layers were combined, washed with brine, dried overNa2SO4, filtered, concentrated and purified by silica gel columnchromatography, using the appropriate heptanes: EtOAc mixture. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere; | Ethyl (E)-4-(benzylamino)-4-oxobut-2-enoate (4a) General procedure: To a solution of fumaric acid monoethyl ester (1.32 g, 9.16 mmol) in THF (20.0 ml) were added SOCl2 (1.33 ml, 18.3 mmol) and DMF (one drop) at 0 °C, and then the resulting mixture was stirred at room temperature for 2.5 h. The solvent was removed under reduced pressure to give the crude acid chloride as a pale yellowish syrup, which was used in the next step without further purification. To a solution of the crude acid chloride in CH2Cl2 (20.0 ml) were added benzyl amine (0.67 ml, 6.11 mmol) and Et3N (3.40 ml, 24.4 mmol) at 0 °C, and the resulting mixture was stirred at room temperature for 15 h. The reaction mixture was quenched with water and extracted three times with CH2Cl2. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography with hexane-EtOAc (2:1 v/v) as an eluent to afford amide 4a (1.23 g, 86%) as a white crystal. | |
With triethylamine In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere; | Ethyl (E)-4-(benzylamino)-4-oxobut-2-enoate (4a). General procedure: To a solution of fumaric acid monoethyl ester(1.32 g, 9.16 mmol) in THF (20.0 mL) were added SOCl2 (1.33 mL, 18.3 mmol) and DMF (one drop) at0 C. The resulting mixture was stirred at room temperature for 2.5 h. The solvent was removed underreduced pressure to give the crude acid chloride as a pale yellowish syrup, which was used in the nextstep without further purification. To a solution of the crude acid chloride in CH2Cl2 (20.0 mL) were added benzylamine (0.67 mL, 6.11mmol) and Et3N (3.40 mL, 24.4 mmol) at 0 C, and the resulting mixture was stirred at room temperaturefor 15 h. The reaction mixture was quenched with water and extracted three times with CH2Cl2. Thecombined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. Theresidue was purified by column chromatography with hexane-EtOAc (2:1 v/v) as an eluent to affordamide 4a (1.23 g, 86%) as white crystals. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54.2% | General procedure: Under an atmosphere of N2, the appropriate amine (0.669 mmol, 1.2 equiv.) was dissolved in 1,2-dichloroethane (DCE) (1 mL) and methyl-(E)-3-(4-formylphenyl)acrylate (106 mg; 0.557 mmol, 1 equiv.) wasthen added, followed by the addition of acetic acid (64 muL, 1.11 mmol, 2 equiv.). The reaction mixture wasstirred overnight at room temperature. When the starting aldehyde had been consumed as monitored by TLC,NaBH(OAc)3 (0.836 mmol, 1.5 equiv.) was added, and the reaction mixture was stirred for 3 h at roomtemperature. The reaction was quenched by the addition of saturated NH4Cl solution (2.0 mL), and thenextracted with saturated sodium hydrogen carbonate solution (10 mL) and ethyl acetate (3 × 10 mL). Theorganic layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The solvent wasremoved in vacuo, and the residue was dissolved in a minimal volume of dichloromethane (DCM) and purifiedby flash column chromatography (silica gel, 20-80% EtOAC:hexane). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With oxygen; copper(II) bis(trifluoromethanesulfonate); potassium iodide In methanol at 60℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere; | To a reaction of H-, 2, 4-triazole-3 -carboxylic acid (226 mg, 2.0 mmol) and 3- methoxybenzylamine (0.28 mL, 2.2 mmol) in dry DMF (10 mL) was added 1- hydroxybenzotriazole monohydrate (337 mg, 2.2 mmol) and EDC (N-(3- Dimethylaminopropyl)-N'-ethylcarbodiimide) (422 mg, 2.2 mmol) followed by N- methylmorpholine (0.88 mL, 8.0 mmol via syringe). The mixture was stirred at room temperature under nitrogen and the solids were gradually dissolved. The contents were stirred at room temperature for 24.0 h, and then slowly diluted into iced water and extracted with DCM (2 x 50 mL). The DCM phase was washed with ice cold water (2 x 100 mL). The DCM phase was dried over anhydrous Na2S04, concentrated under reduced pressure and chromatographed on silica gel using MeOH and DCM (2:98) as eluents to get the desired amide 7 (170.9 mg, 37 % yield) as a white solid compound. -NMR (400 MHz, DMSO-de): <514.76-14.65 (m, 1H), 9.15 (br s, 1H), 8.48 (br s, 1H), 7.23 (t, J= 8 Hz, 1H), 6.90-6.88 (m, 2H), 6.82-6.80 (m, 1H), 4.43 (d, J= 6 Hz, 2H), 3.73 (s, 3H) ppm. MH+ = 233.2 m/z. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22.8% | Stage #1: 3-(aminosulfonyl)-4-chlorobenzoyl chloride With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.25h; Cooling with ice; Stage #2: 3-METHOXYBENZYLAMINE In dichloromethane for 12h; Cooling with ice; | 4.1.2. Synthetic routes of compound a series, B series and X series General procedure: a. 3-sulfonamidobenzoic acid or 4-chloro-3-sulfonamidobenzoicacid (3 mmol) and 30 mL of freshly steamed SOCl2, wererefluxed at 105 °C for 3-5 h. Cooling and standing, then evaporatingthe thionyl chloride under reduced pressure to obtain 3-sulfonyl benzoyl chloride or 4-chloro-3-sulfonyl benzoylchloride;b. The corresponding substituted aromatic amine (0.5 mmol) wasweighed and dissolved in 10 mL of dichloromethane, and 65 mLof base DIPEA (0.5 mmol) was added, and the mixture wasstirred for 15 min in an ice bath. Then, 0.75 mmol of the aboveobtained3-sulfonamidobenzoyl chloride or 4-chloro-3-sulfonamidobenzoyl chloride was added, and the mixture was stirred for 12 h under ice-cooling, and the reaction was monitoredby TLC. After the reaction is terminated, the product isisolated and purified to obtain three series of compounds: A, Band X. |
Tags: 5071-96-5 synthesis path| 5071-96-5 SDS| 5071-96-5 COA| 5071-96-5 purity| 5071-96-5 application| 5071-96-5 NMR| 5071-96-5 COA| 5071-96-5 structure
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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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