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CAS No. : | 16298-03-6 |
Formula : | C6H7N3O2 |
M.W : | 153.14 |
SMILES Code : | C1=CN=C(C(=N1)C(OC)=O)N |
MDL No. : | MFCD00010097 |
InChI Key : | INCSQLZZXBPATR-UHFFFAOYSA-N |
Pubchem ID : | 72669 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
44% | With diiodomethane; isopentyl nitrite In diiodomethane at 85 - 100℃; for 15 h; | Reference Example 15 3-Iodopyrazine-2-carboxylic acid methyl ester (Reference compound No.15-1) Isoamyl nitrite (5.2 mL, 39 mmol) was added to a suspension of 3-aminopyrazine-2-carboxylic acid methyl ester (1.9 g, 12 mmol) in diiodomethane (20 mL) at 85°C, then the mixture was stirred at 100°C for 15 hours. The reaction mixture was allowed to stand and purified by silica gel column chromatography to give 1.4 g of the title reference compound as a pale yellow solid. (Yield 44percent) 1H-NMR(500MHz,CDCl3) δ 4.04(s,3H),8.47(d,J = 2.1 Hz,1H),8.56(d,J = 2.1 Hz,1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With hydrogen bromide; bromine; sodium nitrite; In water; at 0℃; for 0.25h; | Bromine (3.91 g, 24.46 mmol) was added dropwise to a stirred mixture of 3- aminopyrazine-2-carboxylic acid methyl ester (1.27 g, 8.29 mmol) and hydrobromic acid (4.70 mL, 41.5 mmol) at 00C. A solution of sodium nitrite (1.44 g, 20.9 mmol) in water (6 mL) was then added dropwise. The reaction mixture was stirred for 15 min, brought to pH 8 with NaHCO3 (saturated, aqueous), and extracted with ethyl acetate (80 mL) and chloroform (50 mL). The combined organics were dried over MgSO4 and concentrated in vacuoto give 1.13 g (63%) of an orange oil which solidified on standing. |
63% | With hydrogen bromide; bromine; sodium nitrite; In water; at 0℃; for 0.25h; | Bromine (3.91 g, 24.46 mmol) was added dropwise to a stirred mixture of 3- aminopyrazine-2-carboxylic acid methyl ester (1.27 g, 8.29 mmol) and hydrobromic acid (4.70 mL, 41.5 mmol) at 00C. A solution of sodium nitrite (1.44 g, 20.9 mmol) in water (6 mL) was then added dropwise. The reaction mixture was stirred for 15 min, brought to pH 8 with NaHCO3 (saturated, aqueous), and extracted with ethyl acetate (80 mL) and chloroform (50 mL). The <n="47"/>combined organics were dried over MgSO4 and concentrated in vacuo to give 1.13 g (63%) of an orange oil which solidified on standing. LC-MS m/z 217 (M+H+); RT 1.15 mm. |
63% | With hydrogen bromide; bromine; sodium nitrite; In water; at 0℃; for 0.25h; | Bromine (3.91 g, 24.46 mmol) was added dropwise to a stirred mixture of 3- aminopyrazine-2-carboxylic acid methyl ester (1.27 g, 8.29 mmol) and hydrobromic acid (4.70 mL, 41.5 mmol) at 00C. A solution of sodium nitrite (1.44 g, 20.9 mmol) in water (6 mL) was then added dropwise. The reaction mixture was stirred for 15 min, brought to pH 8 with NaHCO3 (saturated, aqueous), and extracted with ethyl acetate (80 mL) and chloroform (50 mL). The combined organics were dried over MgSO4 and concentrated in vacuoto give 1.13 g (63%) of an orange oil which solidified on standing. |
46% | With bromine; sodium nitrite; In chloroform; water; hydrogen bromide; | EXAMPLE 157A Methyl 3-bromopyrazine-2-carboxylate To a rapidly stirring heterogeneous mixture of 3-aminopyrazine-2-carboxylic acid methyl ester (2.00 g, 13.1 mmol) in 48% hydrobromic acid (7.9 mL) cooled to 0 C. was added bromine (2.00 mL, 6.2 g, 38.8 mmol) dropwise over 5 minutes. Then a solution of sodium nitrite (2.27 g, 32.8 mmol) in 9.5 mL of water was added dropwise over 10 minutes. The reaction mixture was stirred at 0 C. for 15-30 minutes and then basified with 60 mL of saturated sodium bicarbonate solution and extracted with ethyl acetate followed by chloroform. The combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained was flash chromatographed on silica gel eluding with mixtures of hexane and ethyl acetate to afford the title compound (1.265 g, 46%). m.p. 43.5-44 C. 1 H NMR (CDCl3, 300 MHz) delta 4.04 (s, 3H), 8.50 (bs, 1H), 8.60 (bs, 1H). MS (DCl/NH3) m/e 217/219 (M+H)+, 234/236 (M+H+NH3)+. |
12% | With tert.-butylnitrite; copper(I) bromide; In acetonitrile; at 60℃; for 0.25h; | Example 81; Synthesis of (3,5-bis-trifluoromethyl-benzyl)- [3-(cycIopentylmethyl-ethyl-amino)- pyrazin-2-ylmethyl]-carbamic acid methyl ester; Step (i): Synthesis of 3-bromo-pyrazine-2-carboxylic acid methyl ester; Copper bromide (1.36 g, 6.1 mmol) and £-butyl nitrite (0.78 g, 7.6 mmol) were added to a 50 mL round bottom flask along with acetonitrile (2 niL), and this mixture was heated at 60 0C for 5 min. After this time, 3-amino-pyrazine-2-carboxylic acid methyl ester (0.8 g, 5.09 mmol) was added portion- wise, with stirring, and stirring was continued at the same temperature for another 10 min. The reaction mixture was then cooled to RT, poured into 100 mL of dilute HCL (2N), and then extracted with diethyl ether (3 x 50 mL). The combined organic layer was washed with dilute HCl, dried over sodium sulfate, and then concentrated under vacuum to afford the title compound (0.139 g), yield: 12 %.1H NMR (CDCl3, 400 MHz): d 8.58 (m, 2H), 4.04 (s, 3H)) ; m/z (CI-MS) 217 (M+) ; IR (neat, cm-1): 3385, 2955, 1742 |
With hydrogen bromide; bromine; sodium nitrite; In water; | (A) Methyl 2-bromo-3-pyrazine carboxylate To a stirred mixture of 12.7 g. of methyl 2-amino pyrazine carboxylate and 47 ml. of 48% hydrobromic acid there was added, dropwise, 12.6 ml. of bromine keeping the temperature at 0. A solution of 14.4 g. of sodium nitrite in 60 ml. of water was then added, dropwise, at 0 and the reaction mixture stirred for 15 minutes. The reaction mixture was basified to pH 8 with sodium bicarbonate and extracted with ethyl acetate and again with chloroform. The organic layers were dried over magnesium sulfate, filtered and concentrated to a yellow oil. Recrystallization from ether-hexane yielded the product, m.p. 43-45 C. | |
With hydrogen bromide; bromine; sodium nitrite; In water; | (A) Methyl 2-bromo-3-pyrazine carboxylate: To a stirred mixture of 12.7 g. of methyl 2-amino pyrazine carboxylate and 47 ml. of 48% hydrobromic acid there was added, dropwise, 12.6 ml. of bromine keeping the temperature at 0. A solution of 14.4 g. of sodium nitrite in 60 ml. of water was then added, dropwise, at 0 and the reaction mixture stirred for 15 minutes. The reaction mixture was basified to pH 8 with sodium bicarbonate and extracted with ethyl acetate and again with chloroform. The organic layers were dried over magnesium sulfate, filtered and concentrated to a yellow oil. Recrystallization from ether-hexane yielded the product, m.p. 43-45 C. | |
With hydrogen bromide; bromine; sodium nitrite; In water; | (A) Methyl 2-bromo-3-pyrazine carboxylate To a stirred mixture of 12.7 g. of methyl 2-amino pyrazine 3-carboxylate and 47 ml. of 48% hydrobromic acid there is added, dropwise, 12.6 ml. of bromine keeping the temperature at 0. A solution of 14.4 g. of sodium nitrite in 60 ml. of water is then added, dropwise, at 0 and the reaction mixture stirred for 15 minutes. The reaction mixture is basified to pH 8 with sodium bicarbonate and extracted with ethyl acetate and again with chloroform. The organic layers are dried over magnesium sulfate, filtered and concentrated to a yellow oil. Recrystallization from ether-hexane yields the product, m.p. 43-45 C. | |
With hydrogen bromide; bromine; sodium nitrite; In water; | (A) Methyl 2-bromo-3-pyrazine carboxylate: To a stirred mixture of 12.7 g. of methyl 2-aminopyrazine 3-carboxylate and 47 ml. of 48% hydrobromic acid there is added, dropwise, 12.6 ml. of bromine keeping the temperature at 0. A solution of 14.4 g. of sodium nitrite in 60 ml. of water is then added, dropwise, at 0 and the reaction mixture stirred for 15 minutes. The reaction mixture is basified to pH 8 with sodium bicarbonate and extracted with ethyl acetate and again with chloroform. The organic layers are dried over magnesium sulfate, filtered and concentrated to a yellow oil. Recrystallization from ether-hexane yields the product, m.p. 43-45 C. | |
With hydrogen bromide; bromine; sodium nitrite; In water; at 0℃; for 2h; | Step 1: synthesis of methyl 3-bromopyrazine-2-carboxylate (99)To a solution of methyl 3-amino-2-pyrazinecarboxylate (13.06 mmol, 2 g) in hydrobromic acid (13.06 mmol, 7.4 ml, 1.057 g) at 0C was added bromine (38.9 mmol, 2 mL, 6.22 g) drop wise and then a solution of sodium nitrite (33.3 mmol, 2.3 g) in water (4 mL). The reaction was stirred for 2h at 0C and the reaction mixture was extracted with CH2CI2. Organic layer was dried and evaporated to give crude methyl 3- bromopyrazine-2-carboxylate 101 (1.2gr, 43%). (m/z) = 217 and 219 (M+H)+. | |
With hydrogen bromide; bromine; sodium nitrite; In water; at 0℃; for 2h; | Step 1: synthesis of methyl 3-bromopyrazine-2-carboxylate (99)[0305]To a solution of methyl 3-amino-2-pyrazinecarboxylate (13.06 mmol, 2 g) in hydrobromic acid (13.06 mmol, 7.4 ml, 1.057 g) at 0 C. was added bromine (38.9 mmol, 2 mL, 6.22 g) drop wise and then a solution of sodium nitrite (33.3 mmol, 2.3 g) in water (4 mL). The reaction was stirred for 2 h at 0 C. and the reaction mixture was extracted with CH2Cl2. Organic layer was dried and evaporated to give crude methyl 3-bromopyrazine-2-carboxylate 101 (1.2 gr, 43%). (m/z)=217 and 219 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With hydrazine hydrate; In ethanol; at 60℃; for 2h;Inert atmosphere; | Hydrazine monohydrate (34 mL, 1094.95 mmol) was added portionwise to a stirred suspension of methyl 3-aminopyrazine-2-carboxylate (21.3 g, 139.09 mmol) in ethanol (65 mL) at r.t. The resulting slurry was stirred at 60 C. for 2 hours, cooled to room temperature and filtered. The solid was washed with cold ethanol (2*25 ml) and dried to a constant weight to afford 3-aminopyrazine-2-carbohydrazide (20.75 g, 97%) as a beige solid: 1H NMR Spectrum; (DMSO-d6) 4.49 (2H, d), 7.46 (2H, br s,), 7.78 (1H, d), 8.17 (1H, d), 9.79 (1H, t); Mass Spectrum [M+H]+=154. |
97% | With hydrazine hydrate; In ethanol; at 20 - 60℃; for 2h; | Hydrazine monohydrate (34 mL, 1094.95 mmol) was added portionwise to a stirred suspension of methyl 3-aminopyrazine-2-carboxylate (21.3 g, 139.09 mmol) in ethanol (65 mL) at r.t. The resulting slurry was stirred at 60 C for 2 hours, cooled to room temperature and filtered. The solid was washed with cold ethanol (2 x 25 ml) and dried to a constant weight to afford 3-aminopyrazine-2-carbohydrazide (20.75 g, 97 %) as a beige solid: 1H NMR Spectrum: (DMSO-d6) 4.49 (2H, d), 7.46 (2H, br s,), 7.78 (IH, d), 8.17 (IH, d), 9.79 (IH, t); Mass Spectrum [M+H]+ = 154. |
97% | With hydrazine hydrate; In ethanol; at 20 - 60℃; for 2h;Inert atmosphere; | Hydrazine hydrate (34 mL, 1.1 mol) was added portionwise to a stirred suspension of methyl 3-aminopyrazine-2-carboxylate 37 (21.3 g, 139 mmol) in ethanol (65 mL) at room temperature. The resulting slurry was stirred at 60 C for 2 h, cooled to room temperature, and filtered. The solid was washed with cold ethanol (2 x 25 mL) and dried to a constant weight to afford 3-aminopyrazine-2-carbohydrazide (20.75 g, 97%) as a beige solid. TBTU (5.77 g, 18.0 mmol) was added portionwise over 15 min to a stirred suspension of DIPEA (8.5 mL, 49 mmol), 1-methylcyclopropanecarboxylic acid (1.63 g, 16.3 mmol) and 3-aminopyrazine-2-carbohydrazide (2.50 g, 16.3 mmol) in acetonitrile (40 mL). The mixture was stirred at 80 C for 20 min, and then cooled to 0 C. DIPEA (8.5 mL, 49 mmol) followed by 4-methylbenzene-1-sulfonylchloride (9.34 g, 49 mmol) were added over a period of 15 min. The reaction mixture was brought to reflux and allowed to stir at room temperature for 14 h. The mixture was concentrated, and the residue was diluted with DCM, washed with water and brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 40% ethyl acetate in dichloromethane. After evaporation of the solvent, the resulting solid was triturated with diethyl ether, filtered, washed with the minimum of diethyl ether and dried to afford 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.12 g, 60%). NBS (1.87 g, 10.5 mmol) was added portionwise to a solution of 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.08 g, 9.6 mmol) in THF (30 mL). The reaction mixture was stirred at room temperature for 16 h and concentrated. The residue was dissolved in dichloromethane (150 mL), washed with water (2 x 40 mL), brine, dried over magnesium sulfate and concentrated. After evaporation of the solvents, the crude product was purified by flash chromatography on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 5-bromo-3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (2.50 g, 88%) as a yellow solid. Bis(triphenylphosphine)palladium(II) chloride (59 mg, 0.08 mmol) was added in one portion to a stirred solution of 5-bromo-3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)pyrazin-2-amine (500 mg, 1.69 mmol) and hexamethyldistannane (0.49 mL, 2.4 mmol) dissolved in dioxane (8 mL) under argon. The resulting suspension was stirred at 80 C for 1 h. The mixture was evaporated. The crude product was purified by flash chromatography on silica gel eluting with 10 to 30% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 3-(5-(1-methylcyclopropyl)-1,3,4-oxadiazol-2-yl)-5-(trimethylstannyl)pyrazin-2-amine 38a (314 mg, 49%) as a yellow crystalline solid. |
Tags: Methyl 3-amino-2-pyrazinecarboxylate | Pyrazines | Amines | Esters | Organic Building Blocks | Heterocyclic Building Blocks | 16298-03-6
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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 |
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