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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: 2-Amino-3-chloropyrazine
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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 6863-73-6 |
Formula : | C4H4ClN3 |
M.W : | 129.55 |
SMILES Code : | C1=CN=C(C(=N1)Cl)N |
Synonyms : |
2-Amino-3-chloropyrazine
|
MDL No. : | MFCD04114305 |
InChI Key : | AEVSSZHXGJAPIE-UHFFFAOYSA-N |
Pubchem ID : | 276224 |
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 |
---|---|---|
68% | A mixture of 3-chloro-pyrazin-2-ylamine (48.7 g, 375.8 mmol) and chloroacetone (120 ml, 1504.5 mmol) was stirred at 90 C for 16 h. in a sealed tube protected from light. After cooling to RT, Et20 was added and the solid formed was filtered off, washed with further Et20, suspended in a saturated solution of sodium carbonate and extracted with DCM. The organic layer was separated, dried (Na2S04), filtered and the solvents evaporated in vacuo. The crude product was precipitated from Et20 to yieldintermediate 4 (43.2 g, 68%) as a white solid which was used in the next step without further purification. m.p. 133.5-138.6 C (WRS-2A). | |
68% | Example A4 8-Chloro-2-methyl-imidazol[1,2-a]pyrazine A mixture of 3-chloro-pyrazin-2-ylamine (48.7 g, 375.8 mmol) and chloroacetone (120 ml, 1504.5 mmol) was stirred at 90 C. for 16 h. in a sealed tube protected from light. After cooling to RT, Et2O was added and the solid formed was filtered off, washed with further Et2O, suspended in a saturated solution of sodium carbonate and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was precipitated from Et2O to yield intermediate 4 (43.2 g, 68%) as a white solid which was used in the next step without further purification. m.p. 133.5-138.6 C. (WRS-2A). | |
68% | at 90℃; for 16h;Sealed tube; Darkness; | A mixture of 3-chloro-pyrazin-2-ylamine (48.7 g, 375 8 mmol) and chloroacetone (120 ml, 1504.5 mmol) was stirred at 90 C. for 16 h. in a sealed tube protected from light. After cooling to RT, Et2O was added and the solid formed was filtered off, washed with further Et2O, suspended in a saturated solution of sodium carbonate and extracted with DCM. The organic layer was separated, dried (Na2SO4), filtered and the solvents evaporated in vacuo. The crude product was precipitated from Et2O to yield intermediate 6 (43.2 g, 68%) as a white solid which was used in the next step without further purification. m.p. 133.5-138.6 C. (WRS-2A). |
53% | at 90℃; for 16h;Sealed tube; | A mixture of 3-chloropyrazin-2-amine (2 g, 15.4 mmol) and 1-chloropropan-2-one (4mL) was heated to 90 C for 16 h in a sealed tube. The reaction mixture was then cooled to roomtemperature and the solid formed was filtered, washed with ether and dried to get the titled compound (1.4 g, 53%). LC-MS: 168.3 [M+Hj. |
7.7% | In methanol; at 88℃;Heating / reflux; | A solution of 2-amino-3-chloropyrazine (1Og, 77.5mmol), chloroacetone (3OmL, 387mmol) in MeOH (25ml_) is refluxed overnight at 88C. It is then stirred for Ih at O0C and any solid that forms, is filtered off and washed twice with MeOH (5ml_). The mother liq. are evaporated, diluted with EtOAc, and washed with HCI 2N, water and brine. The water and HCI mother liq. are evaporated to give a yellow solid that is neutralized with a saturated solution of K2CO3 in water, extracted with DCM, dried with MgSO4 anh. filtered and concentrated. The crude material is purified by column chromatography using a gradient of (DCM/MeOH: 1/0 to 99/1) to give 8-Chloro-2-methyl-imidazo[l,2-a]pyrazine as an orange solid (1.02g, 7.7%). |
at 90℃; for 16h;Sealed tube; | A mixture of 3-chloro-pyrazin-2-ylamine (48.7 g, 375.8 mmol) and chloroacetone (120ml, 1504.5 mmol) was stirred at 90 oc for 16 h. in a sealed tube protected from light. After cooling toRT, Et20 was added and the solid formed was filtered off, washed withfurther Et20, suspended in a saturated solution of sodium carbonate and extracted withDCM. The organic layer was separated, dried (Na2S04), filtered and the solventsevaporated in vacuo. The crude product was precipitated from Et20 to yieldintermediate 6 (43.2 g, 68%) as a white solid which was used in the next step without further purification. m.p. 133.5-138.6 oc (WRS-2A). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Benzyl alcohol (4.55 g, 42.15 mmol) was added under an inert atmosphere dropwise to a suspension of sodium hydride (1. 01 g, 42.13 mmol, 80%) in N-methylpyrrolidinone. Stirring of the reaction mixture was continued for 30 min. 2-Amino-3-chloropyrazine (Compound I in Scheme 1, 5.0 g, 38.6 mmol) was then added in incrememtal portions and the resultant mixture was heated at 80 C for 24 h. The reaction mixture was subsequently cooled and water (200 mL) was added. The aqueous solution was extracted with EtOAc (2 x 40 mL). The combined organic layers were washed with water (2 x 100 mL), dried (Mg04), and concentrated under reduced pressure to obtain a light brown residue. Addition of cold water to the residue, triggered crystallization of the desired product. The crystals were collected and dried over P2O5 (6.33 g, 82%). 1H-NMR (CDCl3) No. 7. 54 (d, J 3.1 Hz, 1H), 7.45-7. 32 (m, 6H), 5. 38 (s, 2H), 4. 78 (br s, 2H); MS (ESI) 202.2 ([M+H] +) | |
53.76% | Sodium hydride (188.6 mg, 4.72 mmol) in N, N- dimethylformamide (3 mL) was slowly added dropwise at room temperature and benzyl alcohol was dissolved in it and it was stirred at room temperature for 1 hour. It was added dropwise slowly to a mixture of 2-amino-3-chloro-pyrazine and heating at 100 C refluxed for 15 hours. After cooling the reaction to room temperature and the solvent was evaporated under reduced pressure and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filter and concentrate under reduced pressure . By separation and purification of the residue by column chromatography (ethyl acetate / n-hexane = 1/4) to obtain the objective compound 300 mg at a yield of 53.76%. | |
53.8% | General procedure: Sodium hydride (60% in mineral oil, 0.04 g, 1 mmol) was addedto a stirred solution of benzyl alcohol derivative (1 mmol) inanhydrous N,N-dimethylformamide (3 mL of DMF) at room temperatureand stirring was continued for 1 h. 2-Amino-3-chloropyrazine (8b, 0.13 g, 1 mmol) was added to the reactionmixture and the reaction mixture was stirred at 100 C for 15 h.After cooling, the solvent was evaporated and the residue waspartitioned betweenwater and dichloromethane. The organic layer was dried over sodium sulfate anhydrous, filtered, and concentrated.The residue was purified by column chromatography (SiO2,EA/n-Hex 1/5). 4.1.2.1 3-(Benzyloxy)pyrazin-2-amine (9g) Yellow solid, yield: 53.8%, 1H NMR (400?MHz, CDCl3) delta?=?5.45 (2H, s, OCH2Ph), 6.20 (2H, br, NH2), 7.38-7.48 (7H, m, ArH). Reported [ 48,49]. |
General procedure: NaH (60% in mineral oil, 0.04 g, 1 mmol) was added to a stirredsolution of the appropriate benzyl alcohol derivative (1 mmol) inanhydrous DMF (3 mL) at room temperature and stirring wascontinued for 1 h. Commercially available 2-amino-3-chloropyrazine (0.13 g, 1 mmol) was added to the reactionmixture which was further stirred at 100 C for 15 h. After cooling,the solvent was evaporated and the residue was partitioned betweenwater and dichloromethane. The organic layer was driedover anhydrous Na2SO4, filtered, and concentrated. The residuewaspurified by flash column chromatography (SiO2, EA/n-Hex 1/5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | A mixture of l-bromo-2, 2-dimethoxypropane (42.4 g, 231.5 mmol) and conc. HC1 (890 uL, 28.9 mmol) in water (6.25 mL) was heated to 90C, for 15 min, cooled to r. t. and quenched with NaHC03. 2-Amino-3-chloropyrazine (Compound I in Scheme 1,0. 2 g, 1.54 mmol) was added and the resultant mixture was heated to 90C for 2h 30 min. The cooled reaction mixture was partitioned between 2M NaHC03 aq (100 mL) and dichloromethane (100 mL). The aqueous layer was separated and extracted with dichloromethane (5 x 100 mL). The combined organic extracts were dried over anhydr. Na2S04 and concentrated in vacuo to yield the crude title compound. Purification by recrystallization from the minimum amount of hot dichloromethane provided 7.0 g (54 % yield) of the pure title compound.'H NMR (CH30H-d4) 8 8. 38 (d, J 4. 5 Hz, 1H), 7.88 (s, 1H), 7.65 (d, J4.5 Hz, 1H), 2.49 (s, 3H); MS (ESI) 167. 8 ([M+H] +, Cl35), 169.8 ([M+H] +, C137) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With sodium methylate; In methanol; | Pre Step A 3-(Methyloxy)-2-pyrazinamine A mixture of 3-chloro-2-pyrazinamine (200 mg, 1.544 mmol) and sodium methoxide (250 mg, 4.63 mmol) in methanol (3.9 ml) was heated to 130° C. via a microwave reactor for 60 min. The crude product mixture was purified by RP-HPLC to give 3-(methyloxy)-2-pyrazinamine (113 mg, 0.903 mmol, 59percent yield). MS (ES+) m/z 125.8 (MH+). |