Structure of 5780-66-5
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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. : | 5780-66-5 |
Formula : | C5H4N2O |
M.W : | 108.10 |
SMILES Code : | N1=C(C=NC=C1)C=O |
MDL No. : | MFCD02179278 |
InChI Key : | DXBWJLDFSICTIH-UHFFFAOYSA-N |
Pubchem ID : | 11274980 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 27.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
42.85 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.33 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.48 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.04 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.73 |
Solubility | 19.9 mg/ml ; 0.184 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.02 |
Solubility | 104.0 mg/ml ; 0.966 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.53 |
Solubility | 3.15 mg/ml ; 0.0292 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.26 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.29 |
* 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 |
---|---|---|
100 mg | With Dess-Martin periodane; In dichloromethane; at 20℃; for 1h; | To a stirred solution pyrazin-2-ylmethanol (500 mg, 4.545 mmol) in DCM (20 ml) was added Dess-martin periodinane (2.89 g, 6.818 mmol) and stirred for 1 hr at RT. Reaction mass was diluted with DCM (100 ml) washed with saturated sodium bicarbonate solution (50 ml X 2) twice. DCM part was separated, dried over sodium sulfate, evaporated to dryness to get 300 mg crude, which was purified by column chromatography using 100-200 silica and 20% EtOAc in hexane as eluent to afford pyrazine-2-carbaldehyde (100 mg) as brown liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Method 54; Pvrazine-2-carboxaldehyde oxime A IN solution of lithium aluminium hydride in THF (73. 8ml, 73.8mmol) was added to a suspension of methyl pyrazine-2-carboxylate (20g, 145mmol) in anhydrous THF (300. 0ml) at-78°C keeping the reaction temperature below-72°C. On completion of addition the reaction mixture was left to stir at-78°C for a further 20 minutes and then quenched with glacial acetic acid (20. 0ml). The resulting mixture was warmed to room temperature and the volatiles removed by evaporation. The residue was dissolved in 3N hydrochloric acid (116ml) and extracted with DCM. The extracts were combined, washed with saturated aqueous sodium hydrogen carbonate solution and the solvent evaporated. The residue was purified by chromatography on silica gel eluting with DCM/diethylether (100: 0 then 80: 20 and then 0: 100) to give pyrazine-2-carboxaldehyde (15.67g, 100percent). This was immediately dissolved in chloroform (200ml) cooled to 0°C and hydroxylamine mono-hydrochloride (11. 02g, 159. 5mmol) and triethylamine (24. 2ml, 117. 4mmol) were added. The reaction mixture was then stirred at ambient temperature for 0.5 hour, and the solvent removed by evaporation. The residue suspended in diethylether (500ml) and the insolubles removed by filtration. The filtrate was evaporated and the residue purified by chromatography eluting with DCM/diethylether (100: 0 then 80: 20 and then 0: 100) to give the title compound (5. 5g, 31percent) as a solid. NMR (DMSO-d6) : 8.15 (s, 1H), 8.62 (dd, 2H), 8. 99 (s, 1H). | |
With lithium aluminium tetrahydride; In tetrahydrofuran; at -78℃; for 1h;Inert atmosphere; | A solution of the product of Example 83A (6.91 g, 50 mmol) in THF (Aldrich, anhydrous, 150 mL) was cooled down to -78° C. and a solution of LiAlH4 (Aldrich, 1.898 g, 50.0 mmol) in THF (50 mL) was added slowly via an additional funnel. The mixture was stirred at -78° C. under N2 for 1 hour, and then it was then carefully and slowly quenched with HOAc (Aldrich, 10 mL) at -70° C. The mixture was slowly warmed up to ambient temperature and stirred for 10 hours. After being concentrated, the residue was stirred with HCl (2N, 15 mL) in CH2Cl2 (300 mL) for 20 minutes and then filtered through diatomaceous earth to remove solid inorganic salt. The organic filtrate solution was concentrated and the residue was dissolved in EtOAc (100 mL) and filtered through diatomaceous earth again. The organic filtrate solution was concentrated to give the titled compound. 1H NMR (300 MHz, DMSO-d6) delta 8.91 (dd, 1H), 8.94 (d, 1H), 9.12 (d, J=1.6 Hz, 1H), 10.08 (s, 1H) ppm; MS (DCI/NH3) m/z 109 (M+H)+. | |
With lithium aluminium tetrahydride; In tetrahydrofuran; at -70℃; for 0.666667h; | LiAlH4 (4g, 100 mMol) was slowly added to a solution of pyrazinecarboxylic acid methyl ester (12. 8g, 100 mMol) in tetrahydrofuran (400 mL) at-70° C. The mixture was stirred at this temperature for 40 min, followed by neutralisation with 20 mL of glacial acetic acid. The solvent was evaporated in vacuo and the residue was partitioned between 30 mL of 2N HCL and dichloromethane. A large amount of brown solid precipitated which was filtered off. The dichloromethane layer was passed through a pad of silica, the solvent was evaporated to give the pyrazine 2-carboxaldehyde (1.4g) as a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With XtalFluor-E; triethylamine tris(hydrogen fluoride); In dichloromethane; at 20℃; | To triethylamine trihydrofluoride (1.956 mL, 12.00 mmol) in DCM (18 mL) at RT were added successively XtalFluor-E (2.061 g, 9.00 mmol) and pyrazine-2-carbaldehyde (0.649 g, 6 mmol). The reaction mixture was stirred overnight at RT. The reaction mixture was quenched with sat. NaHCO3 solution and next extracted with DCM (3x 50 mL), dried (MgSO4) and evaporated under reduced pressure. The product was purified by flash chromatography (100percent DCM) yielding the title compound as a clear oil (703 mg, 90percent).LCMS (Method C): RT = 0.58 mi mlz = 131 [M+H].1H NMR (500 MHz, CDCI3) O 8.95 (s, 1H), 8.74 (s, 1H), 8.65 (s, 1H), 6.71 (t, J 54.7 Hz, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | EXAMPLE 12 Pyrazine carboxaldehyde, O-methyl oxime In a similar manner to that described in Example 7, but starting form pyrazine carboxaldehyde (J. Org. Chem. 37, 111 (1972)), the title compound was obtained in a 60percent yield m.p. 40°-41° C. | |
45% | pyrazine-2-carboxaldehyde After dissolving 2.50 ml of 2,2,6,6-tetramethylpiperidine in 40 ml of tetrahydrofuran, the solution was cooled to -50° C. Next, 5.25 ml of n-butyllithium (2.6 M, n-hexane solution) was added dropwise thereto under a nitrogen atmosphere. The mixture was stirred for 25 minutes, cooled on ice, and stirred for an additional 35 minutes. It was then cooled to -78° C., and a solution of 1.89 g of 2-tert-butoxypyrazine [CAS No.70090-30-1] in tetrahydrofuran (5 ml) was added dropwise. After stirring the mixture for 15 minutes, 1.25 ml of N, N-dimethylformamide was added dropwise. After 10 minutes, water was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (1.00 g, 45percent, yield). 1H-NMR (400 MHz, CDCl3); delta (ppm) 1.68 (9H, s), 8.28 (1H, d, J=2.4 Hz), 8.30 (1H, d, J=2.4 Hz), 10.33 (1H, s). | |
By the procedure of Example 2, using the following carboxaldehydes in place of 2-pyridinecarboxaldehyde:4-pyrimidinecarboxaldehyde2-pyrazinecarboxaldehyde2-pyrrolecarboxaldehyde2-thiazolecarboxaldehyde4-thiazolecarboxaldehyde |
By the procedure of Example 23, using in place of 2-pyridinecarboxaldehyde, the following carboxaldehydes:2-pyrimidinecarboxaldehyde2-pyrrolecarboxaldehyde2-pyrazinecarboxaldehyde4-pyrimidinecarboxaldehyde2-thiazolecarboxaldehyde4-thiazolecarboxaldehyde |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfur; at 110℃; | A mixture of pyrazine-2-carboxaldehyde (1.1 g, 10 mMol), sulphur powder (0.6 g, 18 mMol), and piperidine (3 mL) was stirred at 110° C for 2 hrs. The resultant dark brown mixture was left to stand overnight and then was poured into cold water. The solid was collected by filtration and purified by column chromatography (silica gel, dichloromethane) to give 400 mg of crude thio piperidyl amide as a yellow solid. This was dissolved in methanol (5 mL) and hydrazine hydrate (0.1 mL) was added to the solution. The mixture was stirred at room temperature for 1 hr. More hydrazine hydrate (0.5 mL) was added and the mixture was stirred for 1 hr more. After neutralisation with glacial acetic acid the mixture was extracted with ethyl acetate and dried over MgS04. Isatin (300 mg) and glacial acetic acid (1 mL) were added to the solution and the reaction mixture was heated under reflux overnight. The solvent was evaporated in vacuo and the residue was recrystallised from acetonitrile to give the desired product (130 mg) as a beige solid. |
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