Structure of 127406-08-0
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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.
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CAS No. : | 127406-08-0 |
Formula : | C11H8N2O |
M.W : | 184.19 |
SMILES Code : | O=CC1=CC=C(C=C1)C1=CN=CC=N1 |
MDL No. : | MFCD02684109 |
InChI Key : | QEJFDPPZUXABRM-UHFFFAOYSA-N |
Pubchem ID : | 3853519 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | 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 |
---|---|---|
97% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; for 18h;Heating / reflux; | Step A Ethanol (13 ml) and 1.0M Na2CO3 (27.5 ml) were added to a suspension of 2-chloropyrazine (4.0 g, 34.6 mmole), 4-formylphenylboronic acid (6.8 g, 45.0 mmole), and tetrakis(triphenylphosphine)palladium(0) (2.0 g, 1.7 mmole) in toluene (55 ml). The mixture was refluxed for 18 hours then cooled, diluted with EtOAc, washed with NaHCO3, washed with brine, dried (MgSO4) and concentrated. Purification by chromatography (SiO2, 4:1 hexanes/EtOAc) yielded 6.2 g (97%) of 4-(2-pyrazinyl)benzaldehyde. |
42% | [0410] Step A: [0411] 1M aq. Na2CO3 (20 mL) and ethanol (10 mL) were added to a solution of 2-chloropyrazine (2.30 g, 20.06 mmol), 4-formylphenylboronic acid (3.90 g, 26.01 mmol) and [1,4-bis(diphenylphosphino)butane]palladium(II) dichloride (0.60 g, 0.99 mmol) in toluene (40 mL) and the mixture was heated to reflux for 18 h. The cooled reaction mixture was diluted with ethyl acetate, washed with sat. aq. NaHCO3 and brine, dried (MgSO4), and concentrated. Purification by chromatography (SiO2, 4:1 hexane/ethyl acetate) yielded 1.56 g (42%) of 4-pyrazinylbenzaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
PREPARATION HH7 4-Pyrazin-2-yl-benzaldehyde 1H NMR (400 MHz, CDCl3) delta 10.03 (s, 1H), 9.10 (s, 1H), 8.69 (s, 1H), 8.59 (s, 1H), 8.21 (d, 2H), 8.03 (d, 2H). | ||
Preparation HH7 4-Pyrazin-2-yl-benzaldehyde 1H NMR (400 MHz, CDCl3) delta10.03 (s, 1H), 9.10 (s, 1H), 8.69 (s, 1H), 8.59 (s, 1H), 8.21 (d, 2H), 8.03 (d, 2H). | ||
Preparation 27 4-Pyrazin-2-yl-benzaldehyde 1H NMR (400 MHz, CDCl3) delta 10.03 (s, 1H), 9.10 (s, 1H), 8.69 (s, 1H), 8.59 (s, 1H), 8.21 (d, 2H), 8.03 (d, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Tris(3,6-dioxaheptyl)amine; potassium carbonate; In dichloromethane; water; for 17h;Heating / reflux; | The compound from step A (6.2 g, 33.5 mmole), (1,3-dioxolan-2-yl-methyl)triphenylphosphonium bromide (22.6 g, 52.7 mmole), tris[2-(2-methoxyethoxy)ethyl]amine (11.2 ml, 34.9 mmole), sat. aq. K2CO3 (150 mls), and CH2Cl2 (150 ml) were heated at reflux for 17 hours. The mixture was cooled and the aqueous layer was washed with CH2Cl2 (2×). The combined organic layers were washed with NaHCO3, brine, dried (MgSO4), and concentrated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
820 mg (71%) | With sodium hexamethyldisilazane; In tetrahydrofuran; | Step A 2-[4-[(E)-2-methoxyethenyl]phenyl]-pyrazine Sodium hexamethyldisilazide (10.80 mL, 10.80 mmol, 11.0M in THF) was added to a suspension of methoxymethyltriphenylphosphonium chloride (3.72 g, 10.80 mmol) in THF (20 mL) at -10 C., and the red-orange mixture was stirred for 15 min at -10 C. A solution of 4-pyrazinylbenzaldehyde (1.00 g, 5.43 mmol) prepared as described in reference example 17) in THF (3 mL) was added dropwise, and stirring was continued at -10 C. for 1 h. The reaction mixture was quenched with sat. aq. NH4Cl, extracted with ethyl acetate, the organic layer dried with Na2SO4, and concentrated in vacuo. Purification by medium pressure liquid chromatography (SiO2, 3:1 hexane/ethyl acetate) yielded 820 mg (71%) of the title compound (E:Z=1:1). MS 213 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With C46H49BrClFeN3Pd; copper diacetate; caesium carbonate; In 1,4-dioxane; at 110.0℃; for 24h; | General procedure: A 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n. |
90% | With C46H49BrClFeN3Pd; copper diacetate; caesium carbonate; In 1,4-dioxane; at 110.0℃; for 24h; | General procedure: A 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n. |
90% | With C46H49BrClFeN3Pd; copper diacetate; caesium carbonate; In 1,4-dioxane; at 110.0℃; for 24h; | General procedure: A 10 mL round-bottom flask was charged with the prescribedamount of catalyst Pd/Cu, aryl chlorides (0.5 mmol), phenylboronicacids containing hydroxymethyl (0.75 mmol), Cs2CO3 (1.0 mmol)and dioxane (5 mL) in air. The reaction mixture was then placedin an oil bath and heated at 110 C for 24 h. After removal of thesolvent, the resulting residue was purified by flash chromatographyon silica gel using CH2Cl2 as eluent. The products 4a-k, and4m are known compounds [6,9] except for 4l and 4n. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid; In dimethyl sulfoxide; at 20.0℃; | General procedure: A mixture of HPLC-purified aminooxy-His containing peptide (30 mM in DMSO, 10 muL), aldehyde (30 mM in DMSO, 10 muL) and acetic acid (150 mM in DMSO, 10 muL) was agitated at room temperature (overnight). Crude reaction mixtures were used directly for Plk1 PBD binding ELISA assays. Structures of oxime-containing peptides are shown in Table S1. |
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