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CAS No. : | 1072-98-6 |
Formula : | C5H5ClN2 |
M.W : | 128.56 |
SMILES Code : | NC1=CC=C(Cl)C=N1 |
MDL No. : | MFCD00006324 |
InChI Key : | MAXBVGJEFDMHNV-UHFFFAOYSA-N |
Pubchem ID : | 66174 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
71% | With sulfuric acid; dihydrogen peroxide; at 20℃; for 48h; | [01066] After conc. sulfuric acid (50 ml) was cooled with ice, 30percent aqueous solution of hydrogen peroxide (25 ml) was dropped thereto stirring, and then conc. sulfuric acid (50 ml) solution of 2-amino-5-chloropyridine (5.0 g, 38.9 mmol) was dropped thereto further and stirred for 48 hours at the room temperature. The reaction mixture was added into ice and filtered. The residue was recrystallized with ethanol to obtain 4.38 g (yield 71percent) of 5-chloro-2-nitoropyriine as a colorless powdery crystal. |
With sulfuric acid; dihydrogen peroxide; at 0 - 20℃; for 20h; | Step A: 5-Chloro-2-nitropyridine To concentrated H2SO4 (50 mL) was added 30 percent H202 (25 mL) at 0 °C and a solution of 5- chloropyridin-2-amine (5.0 g, 39 mmol) in concentrated H2S04 (20 mL) was added at 0 °C. The mixture was stirred for 20 hours at room temperature. The mixture was poured into ice water under vigorous stirring and the resulting solid was filtered. The solid was recrystallized from ethanol to give 5-chloro-2-nitropyridine. 1H-NMR (400MHz, CDC13) delta 8.58 (d, J=2.8 Hz, 1H), 8.23 (d, J=8.8 Hz, 1H), 8.00 (dd, J=2.8 Hz, 8.8Hz, 1H). LC/MS m/z 159 (M+l)+. | |
With sulfuric acid; dihydrogen peroxide; In water; at 20℃; for 20h; | Step A: 5-chloro-2-nitropyridine: To concentrated H2SO4 (50 mL) was added 30 percent H2O2 (25 mL) at 0 °C and a solution of 5-chloropyridin-2-amine (5.0 g, 39 mmol) in concentrated H2SO4 (20 mL) at 0 °C. The mixture was stirred for 20 hours at room temperature. The mixture was poured into ice water under vigorous stirring and the resulting solid was filtered. The solid was recrystallized from ethanol to give 5-chloro-2-nitropyridine. |
With sulfuric acid; dihydrogen peroxide; In water; at 0 - 20℃; for 20h; | Step A: 5-chloro-2-nitropyridine: To concentrated H2SO4 (50 mL) was added 30 percent H202 (25 mL) at 0 °C and a solution of 5-chloropyridin-2-amine (5.0 g, 39 mmol) in concentrated H2S04 (20 mL) at 0 °C. The mixture was stirred for 20 hours at room temperature. The mixture was poured into ice water under vigorous stirring and the resulting solid was filtered. The solid was recrystallized from ethanol to give 5-chloro-2-nitropyridine. | |
With sulfuric acid; dihydrogen peroxide; at 0 - 20℃; for 20h; | [0217] To concentrated H2SO4 (50 mL) was added 30 percent H2O2 (25 mL) at 0 °C and a solution of 5-chloropyridin-2-amine (5.0 g, 39 mmol) in concentrated H2SO4 (20 mL) was added at 0 °C. The mixture was stirred for 20 hours at roomtemperature. The mixture was poured into ice water under vigorous stirring and the resulting solid was filtered. The solidwas recrystallized from ethanol to give 5-chloro-2-nitropyridine. 1H-NMR (400MHz, CDCl3) delta 8.58 (d, J=2.8 Hz, 1H),8.23 (d, J=8.8 Hz, 1H), 8.00 (dd, J=2.8 Hz, 8.8Hz, 1H). LC/MS m/z 159 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; water; sodium nitrite; at 10℃; for 0.666667h;Green chemistry; | In a 25 ml reaction flask, first add 3.4 ml of a solution consisting of 17 ml of H2O and 17 ml of concentrated sulfuric acid (50%, volume fraction), then add 1 g (0.01 mol) of 2-amino-5-chloropyridine and cool with an ice salt bath. Below 10 C, after stirring for a few minutes, the reaction solution turned white.Then, a solution consisting of (1.72 g of NaNO2 and 3 mL of H 2 O) was slowly added dropwise, and when it was added dropwise, an irritating gas was generated. After the dropwise addition, the reaction solution became a pale yellow solution, and TCL (thin layer chromatography) was monitored until the reaction was completed ( About 40min).Then, 8 mL of H2O was added, and the reaction was stirred under reflux for 15 min, cooled, and anhydrous Na2CO3 was added under stirring to make the reaction liquid neutral (a yellow-brown solid was produced), filtered, and the obtained filtrate was dried, and then filtered and dissolved with absolute ethanol. The obtained filtrate was dried to give a yellow-brown solid, 5-chloro-2(1H)pyridone, 0.70 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | To a mixture of 2-amino-5-chloropyridine (2.57 g, 20.0 mmol) and sulfuric acid (6.30 ml), huming HNO3 (0.860 ml, 21.1 mmol) was added dropwise over 15 minutes at 55 C and stirred at 55 "C for 1 hour. After cooling, the reaction mixture was poured into ice-water (60 g) and neutralized with aqueous NaOH solution (pH = 11). The precipitated material was collected, washed with H2O and dried under reduced pressure at 50 0C to give 5-chloro-3-nitropyridin-2-amine (2.31 g, 67 %, yellow solid). | |
51.0% | To a 250 mL 3 necked RK flask charged with conc.H2S04 (30 mL) at 0CC, 5 chloropyridin-2-amine (12.5 g) was added portion wise and allowed to stir for 1 h and heated at 50 00 to dissolve starting material completely. Then, conc. HNO3 (8 mL) was added drop wise through addition funnel. The reaction was monitored by every 10 minutes. After completion, 40% sodium hydroxide solution (pH=6-7) was added,the product was extracted with ethyl acetate, washed with water, and dried over anhydrous Na2SO4. The solvent was removed under vacuo to yield the product (11 .0 g, 51.0%) as a pale green solid. LCMS: (M-H) = 172.9 | |
51% | To a 250 mL 3 necked RK flask charged with conc.H2S04 (30 mL) at 000, 5 chloropyridin-2-amine (12.5 g) was added portion wise and solution was allowed to stir for 1 h and heated at 50 00 to dissolve starting material completely. Then, conc. HNO3 (8 mL) was added drop wise to the resulting solution through addition funnel. The reaction was monitored at every 10 minutes. After completion, 40% sodiumhydroxide solution (PH=6-7) was added, the product was extracted with ethyl acetate, washed with water, and dried over anhydrous Na2SO4. The solvent was removed under vacuo to yield the product (11.0 g, 51.0%) as a pale green solid. LOMS: (M-H) = 172.9 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | A solution of 2-amino-5-chloropyridine (2.0 g, 16 mmol) [Matrix Scientific, 021118] in acetone (39 mL) was treated with ethyl bromopyruvate (2.2 mL, 16 mmol) and heated at 60 C for 45 min. The reaction mixture was cooled to 20 C and the suspension was filtered. The solid that was collected was washed with a small amount of cold acetone and dried in vacuo. The solid was diluted with ethanol (12 mL) and water (19 mL), heated at 65 C, and treated with sodium bicarbonate (1.6 g, 19 mmol) portionwise. The reaction mixture was cooled to 20 C and the suspension was filtered. The solid that was collected was washed with water (4 x 80 mL) and dried in vacuo to give the desired product (2.6 g, 74%). LCMS for Ci QHI 0CIN2O2(M+H)+: m/z = 225.1. | |
In 1,2-dimethoxyethane; | Step 1. Ethyl 6-Chloroimidazo[1,2-a]pyridine-2-carboxylate To 2-amino-5-chloropyridine (Aldrich; 2.19 g) in dimethoxyethane (Aldrich; 25 mL) is added ethyl 2-bromopyruvate (Aldrich; 2.37 mL). After stirring overnight, the solid is collected and washed with diethyl ether. The solid is dried under reduced pressure at 45 C. and then is partitioned between dichloromethane and aqueous sodium bicarbonate. The organic phases are dried over sodium sulfate and concentrated to give 3.05 g of ethyl 6-chloroimidazo[1,2-a]pyridine-2-carboxylate. 1 H NMR (CDCl3) delta1.44, 4.46, 7.23, 7.64, 8.16, 8.21. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; nitric acid; | PREPARATION 61 2-Amino5-chloro-3-nitropyridine A procedure similar to that described in Preparation 56 was repeated, except that 25.0 g of 2-amino-5-chloropyridine, 100 ml of concentrated sulfuric acid and 12.5 ml of concentrated nitric acid were used, to give 18.5 g of the title compound, melting at 138-139 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32.47 g (56%) | With aq NaOH; nitric acid; | To 150 mL of conc. H2 SO4 was added 42.96 g (334 mmol) of 2-amino-5-chloropyridine in portions with stirring and cooling (ice-water bath). To the resulting solution was added dropwise 22.5 mL of 69-71% HNO3 (355 mmol) at 50 C. (at such a rate that maintain the temperature within 50-55 C.) over 1 h. The resulting mixture was stirred at 60 C. for 3 h, poured into ice-water (about 1,500 mL) with stirring, then basified to pH 9 by the addition of 40% aq NaOH with stirring and cooling. The precipitate was filtered, washed with water (6*50 mL), and dried to give 32.47 g (56%) of 2 as a yellow powder, mp 190-191 C. (lit. 191-2 C. (Israel, M. & Day, A. R., J. Org. Chem. 24:1455-1460 (1959))). 1 H NMR (DMSO-d6), 8.044-8.055 (m, 3H), 8.054 (d, 1H, J=3.9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitric acid; In water; | 2-Amino-5-chloro-3-nitropyridine (102) Concentrated H2 SO4 (97%, 300 mL) was placed in a 500 mL three-neck round-bottom flask. The flask was equipped with an internal thermometer, a glass funnel and stopper, and placed in a salt/ice bath. When the internal temperature reached 5 C., 2-amino-5-chloropyridine (101) (77.2 g, 0.600 mol) was added over 1 h with stirring. The suspension was then stirred at room temperature to dissolve the rest of the solid. The resulting solution was heated to 55 C. HNO3 (70%, 40.5 mL, d=1.41, 0.634 mol) was added dropwise through an addition funnel as to maintain the internal temperature at 57+-3 C. The reaction solution was poured over ice (1.5 kg), and the resulting mixture partially neutralized with 40% NaOH (~600 mL). The mixture was filtered to leave a yellow/orange solid. This solid was washed by resuspension in water (600 mL). The mixture was filtered, and the resulting solid was dried in the oven for 48 h to yield the title compound as an orange/yellow solid (66.3 g, 63.8%), mp 184-6 C. (Lit., 190-3 C., Vaughan et al., J. Amer. Chem. Soc. 71:1885 (1949)); 1 H NMR (CDCl3): δ6.69 (bs, 2H), 8.33 (d, J=1.5 Hz, 1H), 8.43 (d, J=1.5 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethyl acetate; toluene; | EXAMPLE 14 2-NITRO-5-CHLOROPYRIDINE 2-Amino-5-chloropyridine (50 grams) was added portionwise to a solution of 300 ml. of concentrated H2 SO4 and 150 ml. of 30percent H2 O2, maintained at a temperature of 0°-5° C., over a period of 5.0 hours. The reaction mixture was then allowed to rise to room temperature and stirred at room temperature for 24 hours. The reaction mixture was then poured over ice, and the product residue separated by filtration and air dried. Crystallization from ethyl acetae-ethanol gave only the azo compound. The remainder of the product residue was passed over a column of silica gel with a mixture of 1:1 toluene:ethyl acetate. The desired product was isolated and its identity confirmed by NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A. 3-Amino-N-(5-chloropyridin-2-yl)-6-methylpyridine-2-carboxamide. Using methods substantially equivalent to those described in Example 2-A, 3-amino-N-(5-chloropyridin-2-yl)-6-methylpyridine-2-carboxamide (16 g, 46percent) was prepared from <strong>[39745-40-9]3-amino-2-chloro-6-methylpyridine</strong> and 2-amino-5-chloropyridine. 1H NMR FIA-MS, m/e 263.1 (m+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | In ethanol;Reflux; | To a solution of ethyl formylchloroacetate (2.23 g, 14.8 mmol) in ethanol (60 mL) was added 5-bromopyridin-2-amine (1.90 g, 14.8 mmol), and the mixture was heated to reflux overnight. After cooling, the solvent was removed by rotary evaporation, and the residue was treated with CHC13 (50 mL) and a saturated solution of aqueous NaHC03. The layers were separated and the aqueous layer was further extracted with CHC13 (2 x 30 mL). The combined organic layer was dried over Na2S04, filtered, and concentrated to dryness. Purification by flash column chromatography (20-35% ethyl acetate in hexane) gave the title compound (0.60 g, 18%). LC-MS: single peak at 254 nm, MH+ calcd. for C10H10ClN2O2: 225, obtained: 225. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.2% | With pyridine; In dichloromethane; at 0 - 25℃; for 0.5h; | [00156] Acid chloride obtained from Step 1, was taken up in dichioromethane (20 mL) and a solution of 2 (11.5 mmols, 1.9 g, 0.9 eq) and triethyl amine (38.2 mmols, 3.86 g, 3.0 eq) in dichloromethane (10 mL) was added dropwise at 0 °C. The reaction was stirred at 25 °C for 30 mm. The reaction progress was monitored by TLC. It was then diluted with dichloromethane, and washed successively with saturation solution ammonium chloride, saturation solution sodium bicarbonate and brine. The crude product was purified by silica gel chromatography (Petroleum ether/ethyl acetate, 4/1) to give the desired product 14 (2.00 g, 6.53 mmols, 5 1.3percent) as a white solid.: [00161] Compound 30 was similarly prepared as the synthesis of Intermediate 14, while in Step 2, pyridine was used as the base and solvent. Yield: 44.2percent |
Tags: Edoxaban Impurity 37 | Pyridines | Chlorides | Amines | Organic Building Blocks | Heterocyclic Building Blocks | 1072-98-6
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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 |
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