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CAS No. : | 20265-38-7 | MDL No. : | MFCD00833386 |
Formula : | C6H8N2O | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | YXFAOWYMDGUFIQ-UHFFFAOYSA-N |
M.W : | 124.14 | Pubchem ID : | 2737488 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | |
Hazard Statements: | H302+H312+H332-H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
92% | With hydrogen;palladium 10% on activated carbon; In methanol; for 4h; | (1)10percent palladium-activated carbon (2.5 g) was added to a solution of commercially available <strong>[20265-35-4]2-methoxy-3-nitropyridine</strong> (50.5 g) in methanol (500 mL), and the mixture was stirred for four hours in a hydrogen atmosphere.The reaction solution was filtered through celite, and then the filtrate was concentrated under reduced pressure.The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1) to give 2-methoxypyridin-3-amine as a yellow powder (37.2 g, 92percent).1H NMR (300 MHz, CDCl3) delta ppm 3.64-3.88 (m, 2H), 3.92-4.05 (m, 3H), 6.67-6.76 (m, 1H), 6.84-6.92 (m, 1H), 7.54-7.62 (m, 1H).MS(+): 125 [M+H]+. |
90% | palladium-carbon; In ethanol; | EXAMPLE 13 Synthesis of 2-methoxy-3-aminopyridine STR28 To a solution of the compound of Example 12 (17.12 g, 0.11 mol) in ethanol (180 mL) in a Parr bottle, was added 4percent Pd/C (3.43 g). The bottle was sealed, purged with nitrogen and was pressurized (5 psi) with hydrogen. After stirring at room temperature for 2 hr, the reaction vessel was vented, purged with nitrogen and filtered. The clear filtrate was concentrated to give the title compound (15.3 g, 90percent). 1 H NMR (CDCl3): 7.58 (dd, J=5, 2 Hz, 1H); 6.87 (dd, J=8, 2 Hz, 1H); 6.72 (dd, J=8, 5 Hz, 1H); 3.98 (s, 3H). |
87% | With hydrogen;palladium 10% on activated carbon; In methanol; for 15h; | A solution of 2- methoxy-3-nitro-pyridine (70. g, 0.45 mol) in methanol (700 mL) containing palladium on carbon (7 g, 10 percent) was stirred under an atmosphere of hydrogen for 15 hours. The catalyst was filtered and washed with methanol. The filtrate was evaporated to dryness to give crude 2- methoxy-pyridin-3-ylamine (48 g, 0.39 mol, 87 percent), which was used directly in the next step. |
74% | With hydrogen;palladium 10% on activated carbon; In methanol; | Compound 1 (20.8 g, 135 mmol) was dissolved in methanol (270 mL) and palladium on carbon (10percent Pd dry weight basis, Degussa type E101 NE/W, 50percent water content, 5.75 g, 2.7 mmol Pd) was added. The atmosphere was replaced with hydrogen (toggle between vacuum and hydrogen from a balloon five times), the mixture was stirred overnight, then filtered. The filtrate was concentrated under vacuum and the residue was taken up in a 1:1 hexanes:ethyl acetate mixture and washed with a 4:1 mixture of water and saturated NaHCO3, saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and filtered and the filtrate was concentrated under reduced pressure to give compound 2 (12.43 g, 74percent) as a white solid. This material was used without purification. |
38.9 g | With palladium 10% on activated carbon; hydrogen; In methanol; for 3h; | A solution of <strong>[20265-35-4]2-methoxy-3-nitropyridine</strong> (50 g, 324.4 mmol) and 10percent Pd/C (5 g) in MeOH (500 ml_) was stirred under an atmosphere of H2 for 3 h. The mixture was filtered through celite and the filter was washed with MeOH. The filtrate was concentrated in vacuo to yield 2-methoxypyridin-3-amine as a brown solid (38.9 g, 313.4 mmol). 1H NMR: (300 MHz, CDCI3) delta: 3.74 (br. s, 2H), 3.96 (s, 3H), 6.72 (m, 1 H), 6.86 (m, 1 H), 7.56 (d, J=1.8, 1 H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In 1,4-dioxane; for 4h;Reflux; | A 2000ml reaction vessel was charged with 2-methoxypyridin-3-amine 41 (100g, 0.8mol, 1wt), di-tert butyl dicarbonate (194g, 0.89mol, 1.94wt) and 1,4-dioxane (1140ml, 11.4vol). The reaction mixture was heated at reflux until complete (approx. 4 hours) as indicated by the absence of starting material by TLC analysis (eluent=1:4 ethyl acetate:hetanes, Rf starter 0.3; Rf product 0.55). The reaction mixture was concentrated to give the title compound as a dark oil (181g, 100%th.).1H NMR (400MHz, DMSO): d 1.47 (s, 9H), 3.91 (s, 3H), 6.95 (m, 1H), 7.84 (m, 1H), 7.98 (d, J=8.1Hz, 1H), 8.17 (br s, 1H). |
90.2% | 3.72 g (30 mmol) of 2-methoxy-3-pyridylamine in solution in 30 ml of tetrahydrofuran are placed in a 100-ml reactor, protected from moisture, and under a nitrogen atmosphere, and then 60 ml (60 mmol) of sodium bis(trimethylsilyl)amide in a 1 M solution in tetrahydrofuran are added dropwise at room temperature. After stirring the reaction mixture for 20 minutes at room temperature, 6.54 g (30 mmol) of di-tert-butyl carbonate are added dropwise to the reaction medium kept at room temperature. After stirring at room temperature for 3 hours, the tetrahydrofuran is evaporated off.. The residue is taken up in ethyl acetate, washed with water, with hydrochloric acid (0.1 M) and then with water (until a PH of the washings equal to 7 is obtained).. After drying the organic phase over sodium sulfate, and evaporation of the solvent, a black oil is obtained which is chromatographed on a silica gel (eluent ethyl acetate-hexane: 1-3).. After evaporation of the solvent, 6.1 g of an amber-coloured oil are obtained, that is to say a yield of 90.2%. TLC: (MERCK "Kieselgel 60" silica gel; AcOEt-hexane: 1-2); Rf=0.4 I.R.: upsilon NH=3425, CO=1731; NMR: (CDCl3): 1.5 (s, 9H); 3.95 (s, 3H); 6.8 (dd, 1H, J=5 Hz, J=7.8 Hz); 6.9 (s, 1H); 7.7 (dd, 1H, J=5 Hz, J=1.6 Hz); 8.2 (d, 1H, J=7.8 Hz). | |
3.9 g (87%) | With hydrogenchloride; In tetrahydrofuran; ethyl acetate; | A) Preparation of 3-(tert-Butoxycarbonylamino)-2-methoxypyridine STR12 To a stirred solution of 2.48 g (20 mmol) of 3-amino-2-methoxypyridine and 4.37 g (20 mmol) of di-tert-butyldicarbonate (Boc2 O) in 10 mL of THF was added at 0 C. 40 mL of a 1M solution of NaHMDS in THF. The mixture was then stirred at room temperature for 2 hours. The THF was removed by rotary evaporation and the residue was dissolved in EtOAc and washed twice with an equal volume of 0.1N HCl. The EtOAc layer was dried (MgSO4) and concentrated to give 3.9 g (87%) of the desired material as an oil after purification further by flash chromatography on silica gel using 95:5 hexane:EtOAc as the eluant. |
In 1,3-dioxane; for 24h;Heating / reflux; | 3-Amino-2-methoxyisonicotinic acid (1) Production of t-butyl (2-methoxypyridin-3-yl)carbamate: 2-methoxypyridine-3-amine (7.0 g, 56.4 mmol) and di-t-butyl dicarbonate (18.5 g, 84.6 g) were dissolved in 1,3-dioxane (20 mL), and heated under reflux for 24 hours. The solvent was evaporated off to obtain the intended, pale yellow oily compound (13.1 g). | |
In 1,4-dioxane; at 110℃;Inert atmosphere; | Under a nitrogen atmosphere, 50.0 g of 2-methoxy-3-aminopyridine (I) (0.4 mol, 1.0 eq) was sequentially added to the reaction bottle.105.5g of di-tert-butyl dicarbonate (0.48mol, 1.2eq) and 250mL of 1,4 dioxane, stir to dissolve.The temperature was raised to 110 C and the reaction was stirred overnight. The plate was controlled and the raw material reaction was complete.Distillate to no fraction under reduced pressure, add n-heptane, and wash twice with saturated sodium bicarbonate.It was distilled under reduced pressure until no fraction was added, and tetrahydrofuran was added to obtain a tetrahydrofuran solution of compound II. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | Example 215 N-(2-Methoxypyridin-3-yl)-5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzamide 3-Amino-2-methoxypyridine (0.149 g, 1.203 mmol), triethylamine (0.122 g, 1.203 mmol) and <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> (0.203 g, 1.203 mmol) were added to a methylene chloride solution (150 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.300 g, 0.802 mmol) and the resulting solution was stirred at room temperature for 4 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform: methanol = 50:1) to obtain the titled compound (0.250 g, 0.520 mmol, 65percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; | Under a nitrogen atmosphere, 50.0 g of 2-methoxy-3-aminopyridine (I) (0.4 mol, 1.0 eq), 122.2 g of triethylamine (1.2 mol, 3.0 eq), and 250 mL of tetrahydrofuran were added to the reaction bottle in turn, and the solution was stirred clear.65.6g of tert-butyl chloroformate (0.48mol, 1.2eq) was added dropwise at a temperature of 0-10 C.After the addition is completed, the temperature is raised to room temperature and stirred overnight for reaction.Distill under reduced pressure to no fraction, add n-heptane, and wash twice with water.After distillation under reduced pressure to no fraction, tetrahydrofuran was added to obtain a tetrahydrofuran solution of compound (II). |
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