Structure of 5521-56-2
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CAS No. : | 5521-56-2 |
Formula : | C5H7N3 |
M.W : | 109.13 |
SMILES Code : | CC1=CN=CC(=N1)N |
MDL No. : | MFCD08235193 |
InChI Key : | UAOOJJPSCLNTOP-UHFFFAOYSA-N |
Pubchem ID : | 12236939 |
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 |
---|---|---|
71% | With ammonia In water at 180℃; for 8 h; sealed vessel | 60ml) at O0C was added, diethylmalonate (2.1moleq) in THF (60ml) and 2,6- dichloropyrazine (2Og) in THF (40ml). The mixture was then heated to reflux for 18hrs before being allowed to cool and 2M Hydrochloric acid (100ml) added. The resulting two layers were separated and the THF layer partially concentrated under vacuum to give a solution containing 2-(6-chloro-pyrazin-2-yl)-malonic acid diethyl ester. This solution was EPO <DP n="6"/>then cooled to 100C and 2M sodium hydroxide (328ml) added. After stirring for 24hrs the mixture was washed with methyl isobutyl ketone [MIBK] (200ml) and the organic layer discarded. The aqueous layer containing 2-(6-chloro-pyrazin-2-yl)-malonic acid was then added to 6M hydrochloric acid (135ml), maintaining a reaction temperature of 20-25°C to facilitate the decarboxylation.The resulting 6-chloro-pyrazin-2-yl-acetic acid partially precipitated from the mixture, but for ease of isolation was extracted into MIBK (130ml), dried using MgSO4, filtered and evaporated to give a yellow solid. The resulting crude solid 22.4g was then crystallised from methyl-t-butyl ether (MTBE) to give pure 6-chloro-pyrazin-2-yl-acetic acid , 15.4g 67percent yield based on 2,6-dichlorpyrazine.The 6-chloro-pyrazin-2-yl-acetic acid (20.Og) was then treated with aqueous ammonia (120ml) in a sealed vessel at 180°C (35 bar) for 8hrs. The mixture was then cooled to 20°C and water (40ml) added, before being concentrated under vacuum to remove the ammonia. The product was extracted into ethyl acetate and the solution treated with charcoal, before being dried using MgSO4, filtered and evaporated to give 6-methyl-2-pyrazin-2-ylamine as a pale green solid 9.Og, 71percent yield based on 6-chloro-pyrazin-2-yl-acetic acid. Analysis 2-(6-Chloro-pyrazin-2-yl)-malonic acid diethyl esterMS (EI +ve) 273/275 (M+H) IH NMR (CDCl3) :δ 8.7 (IHs), 8.5 (IHs), 4.9 (IHs), 4.2(2x2Hq), 1.2 (2x3Ht).6- Chloro-pyrazin-l-yl-acetic acidMS (EI +ve) 173/175 (M+H)IHNMR (CDCl3) :δ 8.55 (IH s), 8.50 (IH s); 3.9 (2Hs).6-Methyl-2-pyrazin-2-ylamine MS (GC/MS) : 100percent RT 2.0mins, M+H = 110IHNMR (CDC13) : δ 7.8 (IHs), 7.8 (IHs), 4.4 (2H bs), 2.4 (3Hs). Mpt : 124-1250C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | at 105℃; for 16.25 h; | A. 6-Methylpyrazine-2-ylamine. To a solution containing 6-chloro-2- pyrazineamine (5.0 g, 38.75 mmol) in 1,4-dioxane (70 mL) was added [1,3- bis(diphenylphosphino]Ni(II)Cl2 (2.10 g, 38.76 mmol), followed by drop-wise addition of dimethylzinc in toluene (38.75 mL, 2.0 M, 77.50 mmol), over 15 min. The solution was allowed stir at 105 °C for 16 hours. The solution was then condensed under reduced pressure, diluted with ethyl acetate and filtered through celite to remove the nickel salts. The resultant slurry was purified via Biotage silica gel chromatography (0-8percent methanol in dichloromethane) to afford the title compound as an orange solid (1.18 g, 28percent yield). MS (ESI) m/z 1 10.3 [M+ 1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | [1,3- bisdiphenylphosphino]Ni(II)Cl2; In 1,4-dioxane; toluene; at 105℃; for 16.25h; | A. 6-Methylpyrazine-2-ylamine. To a solution containing 6-chloro-2- pyrazineamine (5.0 g, 38.75 mmol) in 1,4-dioxane (70 mL) was added [1,3- bis(diphenylphosphino]Ni(II)Cl2 (2.10 g, 38.76 mmol), followed by drop-wise addition of dimethylzinc in toluene (38.75 mL, 2.0 M, 77.50 mmol), over 15 min. The solution was allowed stir at 105 °C for 16 hours. The solution was then condensed under reduced pressure, diluted with ethyl acetate and filtered through celite to remove the nickel salts. The resultant slurry was purified via Biotage silica gel chromatography (0-8percent methanol in dichloromethane) to afford the title compound as an orange solid (1.18 g, 28percent yield). MS (ESI) m/z 1 10.3 [M+ 1]+. |
1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In tetrahydrofuran; diethyl ether; for 3h; | Example 29: Preparation of:2-(4-Ch]oro-2-mophiholin-4-yl-1.24hiazol-5-yl)-5-(dicvcloprorhoyImethylV3,7-dimethyl-5H-pyitauolof2.3- ipyrazine; Part A: 2-Amino-6-methy] pyrazine; A solution of zinc chloride (2.0M in THF, 96.5 mL, 48.2 mmol, 5.0 equiv.) is treated dropwise with methylmagnesium bromide (3.0 M in Et2O, 32.2 mL, 96.5 mmoi, 10.0 equiv.) at 0 °C. The mixture is wanned to room temp and stirred for 45 min. A solution of 2-amino-6-chloro pyrazine (1.25 g. 9.65 mmol, 1.0 equiv) and NiC12(dppp) (157 mg, 0.29 mmol, 0.03 equiv) in THF (15 mL) is added to the freshly prepared dimethylzinc reagent. The reaction mixture is stirred under for 3h and cooied to room temp. The reaction is quenched carefully with sat'd NH4CI solution and allowed to stir overnight. The layers are separated and the aqueous layer is extracted with EtOAc (2 X 30 mL). The combined organic extracts are washed with brine, dried over Na2Spsi4 and concentrated under reduced pressure to give a cream-colored solid that is used without further purification. MS = 110.08 (M +1). 1H NMR (400 MHz, CDCI3) delta 7.78 (IH, s), 7.72 (IH, s), 4.59 (2H, bs), 2.35 (3H, s). | |
With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In 1,4-dioxane; toluene; at 20 - 95℃;Inert atmosphere; | Following a literature procedure (Walters, I. A. S. Tetrahedron Lett. 2006, 47, 341), a solution of dimethylzinc (2.0 M in toluene, 75.0 mL, 150.0 mmol) was carefully added in 25 mL portions to a solution of <strong>[33332-28-4]2-amino-6-chloropyrazine</strong> (10.0 g, 77.0 mmol) and 1,3-bis(diphenylphosphino)propane-nickel (II) chloride (4.2 g, 7.8 mmol) were dry in dioxane (400 mL) under a nitrogen atmosphere. The reaction was stirred at rt for 2 h and then heated to 50° C. for 1 h and 95° C. overnight. The reaction was allowed to cool to rt and an additional charge of dimethylzinc was added (22 mL, 44 mmol) and the reaction was then maintained at 95° C. overnight. The reaction was cooled to rt, quenched over 15 min with MeOH and then concentrated to a brown solid. Water and EtOAc were added to the solid, and the mixture was sonicated. The solid was removed by filtration and brine was added to the EtOAc-water mixture. The layers were separated, and the organic layer was dried (Na2SO4), and concentrated to give 9.72 g (?70 purity) of 6-methylpyrazin-2-amine, which was carried forward without further purification: LCMS (m/z): 110.0 (MH+), tR=0.21 min. |
Intermediate 1 : 6-Methyl-2-pyrazinamine <n="27"/>; Dimethyl zinc (15.44 ml, 30.9 mmol) was added to a solution of 6-chloro-2- pyrazinamine (2 g, 15.44 mmol) and NiCI2(dppp) (0.837 g, 1.544 mmol) in dry 1 ,4- dioxane (75 ml) and the mixture was refluxed for 24 hours. The mixture was then cooled to room temperature, quenched with methanol and concentrated in vacuum. The residue was partitioned between EtOAc and brine. The organic phase was dried over Na2SO4, filtered and the solvent evaporated. The residue was purified by silica chromatography (MeOH-NH3-DCM) to afford the title compound as a pale yellow solid. | ||
1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In 1,4-dioxane; toluene; at 20 - 95℃;Inert atmosphere; | Following a literature procedure (Walters, I.A.S. Tetrahedron Lett. 2006, 47, 341), a solution of dimethylzinc (2.0 M in toluene, 75.0 mL, 150.0 mmol) was carefully added in 25 mL portions to a solution of <strong>[33332-28-4]2-amino-6-chloropyrazine</strong> (10.0 g, 77.0 mmol) and l ,3-bis(diphenylphosphino)propane-nickel (II) chloride (4.2 g, 7.8 mmol) were <n="119"/>dry in dioxane (400 mL) under a nitrogen atmosphere. The reaction was stirred at rt for 2 h and then heated to 50 0C for 1 h and 95 0C overnight. The reaction was allowed to cool to rt and an additional charge of dimethylzinc was added (22 mL, 44 mmol) and the reaction was then maintained at 95 0C overnight. The reaction was cooled to rt, quenched over 15 min with MeOH and then concentrated to a brown solid. Water and EtOAc were added to the solid, and the mixture was sonicated. The solid was removed by filtration and brine was added to the EtO Ac-water mixture. The layers were separated, and the organic layer was dried (Na2SO^, and concentrated to give 9.72 g (~70 purity) of 6-methylpyrazin-2-amine, which was carried forward without further purification: LCMS (m/z): 110.0 (MH+), R = 0.21 min. | |
1,3-bis[(diphenylphosphino)propane]dichloronickel(II); In 1,4-dioxane; for 18.5h;Heating / reflux; | Dimethylzinc (lOOmL of a 2M solution in toluene) was added dropwise over 0.5h to astirred solution of 6-chloro-2-pyrazinamine (12.9g) and [1,3-fe(diphenylphosphmo)propane]nickel(n) chloride (5.4g) in dioxane (200mL) under anitrogen atmosphere. The reaction mixture was heated at reflux for 18h, then cooled toroom temperature and quenched cautiously with zso-propanol (30mL) and methanol(50mL). After removal of solvent in vacua, the residue was partitioned betweendichloromethane and aqueous ammonium chloride. The organic phase was filtered throughcelite, dried (MgSO4), filtered and evaporated to give the crude product as an orange solid.Chromatography on silica gel eluting with ethyl acetate/methanol mixtures gave the sub- title compound (5.1g). Used directly. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of anhydrous zinc(II) chloride (26.3 g, 193 mmol) in THF (150 mL) at 0° C., was added 3M methyl magnesium bromide in diethyl ether (129 mL) drop wise over a period of 1 h. [1,3-bis(diphenylphosphino)propane] nickel(II) chloride (2.08 g, 3.85 mmol) was then added and the mixture allowed to warm to room temperature. To the above mixture, a solution of <strong>[33332-28-4]6-chloro-2-aminopyrazine</strong> (5.00 g, 38.6 mmol) in anhydrous THF (25 mL) was added and the reaction stirred, under a nitrogen atmosphere, at reflux for 6 h. After this time, the mixture was cooled to room temperature, then to 0° C. and carefully quenched with saturated aqueous ammonium chloride (50 mL). The organic layer was separated and dried over sodium sulfate. The drying agent was filtered and the filtrate concentrated under reduced pressure to provide crude 6-methylpyrazin-2-amine VI, which was used in the next step without purification: 1H NMR (400 MHz, CDCl3) delta: 7.63 (s, 1H), 7.53 (s, 1H), 4.96 (bs, 2H), 2.16 (s, 3H). | ||
To a solution of anhydrous zinc(II) chloride (26.3 g, 193 mmol) in THF (150 mL) at 0 °C, was added 3M methyl magnesium bromide in diethyl ether (129 mL) drop wise over a period of 1 h. [l,3-bis(diphenylphosphino)propane] nickel(II) chloride (2.08 g, 3.85 mmol) was then added and the mixture allowed to warm to room temperature. To the above mixture, a solution of <strong>[33332-28-4]6-chloro-2-aminopyrazine</strong> (5.00 g, 38.6 mmol) in anhydrous THF (25 mL) was added and the reaction stirred, under a nitrogen atmosphere, at reflux for 6 h. After this time, the mixture was cooled to room temperature, then to 0 °C and carefully quenched with saturated aqueous ammonium chloride (50 mL). The organic layer was separated and dried over sodium sulfate. The drying agent was filtered and the filtrate concentrated under reduced pressure to provide crude 6- methylpyrazin-2-amine VI, which was used in the next step without purification: 1H NMR (400 MHz, CDC13) delta: 7.63 (s, 1H), 7.53 (s, 1H), 4.96 (bs, 2H), 2.16 (s, 3H). | ||
With 1,3-bis[(diphenylphosphino)propane]dichloronickel(II); zinc(II) chloride; In tetrahydrofuran; diethyl ether; at 0 - 20℃; for 6h;Inert atmosphere; Reflux; | [0279] 6-Methylpyrazin-2-amine VI: To a solution of anhydrous zinc(II) chloride (26.3 g, 193 mmol) in THF (150 mL) at 0 °C, was added 3M methyl magnesium bromide in diethyl ether (129 mL) drop wise over a period of 1 h. [1,3- Bis(diphenylphosphino)propane]nickel(II) chloride (2.08 g, 3.85 mmol) was then added and the mixture allowed to warm to room temperature. To the above mixture, a solution of <strong>[33332-28-4]6-chloro-2-aminopyrazine</strong> (5.00 g, 38.6 mmol) in anhydrous THF (25 mL) was added and the reaction stirred, under a nitrogen atmosphere, at reflux for 6 h. After this time, the mixture was cooled to room temperature, then to 0 °C and carefully quenched with saturated aqueous ammonium chloride (50 mL). The organic layer was separated and dried over sodium sulfate. The drying agent was filtered and the filtrate concentrated under reduced pressure to provide crude 6-methylpyrazin-2 -amine VI (2.60 g, 62percent) as a light yellow solid which was used in the next step without purification: NMR (400 MHz, CDC13) delta: 7.63 (s, 1H), 7.53 (s, 1H), 4.96 (bs, 2H), 2.16 (s, 3H). |
To a solution of anhydrous zinc(II) chloride (26.3 g, 193 mmol) in THF (150 mL) at 0 °C, was added 3M methyl magnesium bromide in diethyl ether (129 mL) drop wise over a period of 1 h. [l ,3-bis(diphenylphosphino)propane] nickel(II) chloride (2.08 g, 3.85 mmol) was then added and the mixture allowed to warm to room temperature. To the above mixture, a solution of <strong>[33332-28-4]6-chloro-2-aminopyrazine</strong> (5.00 g, 38.6 mmol) in anhydrous THF (25 mL) was added and the reaction stirred, under a nitrogen atmosphere, at reflux for 6 h. After this time, the mixture was cooled to room temperature, then to 0 °C and carefully quenched with saturated aqueous ammonium chloride (50 mL). The organic layer was separated and dried over sodium sulfate. The drying agent was filtered and the filtrate concentrated under reduced pressure to provide crude 6-methylpyrazin-2- amine VI, which was used in the next step without purification: XH NMR (400 MHz, CDC13) delta: 7.63 (s, 1H), 7.53 (s, 1H), 4.96 (bs, 2H), 2.16 (s, 3H). |
Tags: 5521-56-2 synthesis path| 5521-56-2 SDS| 5521-56-2 COA| 5521-56-2 purity| 5521-56-2 application| 5521-56-2 NMR| 5521-56-2 COA| 5521-56-2 structure
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H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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