Structure of 89283-32-9
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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. : | 89283-32-9 |
Formula : | C5H5ClN2O |
M.W : | 144.56 |
SMILES Code : | OCC1=C(Cl)N=CC=N1 |
MDL No. : | MFCD11977628 |
InChI Key : | NYTVRJQDIXLFAT-UHFFFAOYSA-N |
Pubchem ID : | 40152213 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.2 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 33.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.01 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.47 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.41 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.09 |
Solubility | 11.6 mg/ml ; 0.0805 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.4 |
Solubility | 57.1 mg/ml ; 0.395 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.08 |
Solubility | 1.22 mg/ml ; 0.00841 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 |
Yes |
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 |
0.0 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) |
1.86 |
* 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 |
---|---|---|
31% | 3-Chloropyrazine-2-carboxylic acid (2.97 g, 18.73 mmol, 1 eq.) was dissolved in tetrahydrofuran (75 mL). The solution was stirred in an ice bath and triethylamine (5.2 mL, 37.5 mmol, 2 eq.) was added followed by addition of methyl chloroformate (1.74 mL, 22.5 mmol, 1.2 eq.) dropwise. After 30 m, the reaction was filtered and the solid rinsed with more tetrahydrofuran (10 mL). The tetrahydyofuran solution was stirred in an ice bath and a suspension of sodium borohydride (1.4 g, 37.5 mmol, 2 eq.) in water (3 mL) was added. After 1 h, a saturated aqueous ammonium chloride solution (100 mL) was added to the reaction and the mixture was extracted with ethyl acetate (2 x 100 mL). The combined organic phases were washed with a saturated aqueous sodium chloride solution (25 mL) and dried over sodium sulfate. After filtration and evaporation, the residue was purified by silica gel chromatography (5 - 70percent ethyl acetate/hexanes) to give (3-chloropyrazin-2-yl)methanol (0.84 g, 31percent) as a faintly colored oil. | |
22% | 102901 To a solution of <strong>[27398-39-6]3-chloropyrazine-2-carboxylic acid</strong> (2.0 g, 12.70 mmol, 1.0 eq.) andTEA (3.50 mL, 25.40 mmol, 2.0 eq.) in THF (50 mL) was added methyl chloroformate (1.2 mL,15.20 mmol, 1.2 eq.) atO °C. The mixture was stirred at 0°C for 10 mm and filtered. To thisfiltrate was added a suspension of NaBH4 (0.97 g, 25.40 mmol, 2 eq.) in water (1.0 mL) at 0 °C. The mixture was stirred at 0 °C for 1 h, quenched with NH4C1 (aq) solution, and extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give (3-chloropyrazin-2- yl)methanol (400 mg, 22percent) as a white solid. 1H NMR (400 MHz, MeOD) 8.58 (d,J 2.5 Hz,1H), 8.38 (d,J= 2.5 Hz, 1H), 4.84 (s, 2H). LRMS (M+H+) m/z 145.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tetrahydroborate; In methanol; at 20℃; for 1h; | To a solution of <strong>[121246-96-6]3-chloropyrazine-2-carbaldehyde</strong> (700mg, 4.91 mmol) in methanol (10ml) was dropwise NaBH4 (223mg, 5.89mmol). The reaction mixture was stirred at room temperature for 1 hr, and the reaction was terminated with a saturated aqueous ammonium solution, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in a vacuum. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | Step 1 To a solution of <strong>[27398-39-6]3-chloropyrazine-2-carboxylic acid</strong> (2.0 g, 12.70 mmol, 1.0 eq.) and TEA (3.50 mL, 25.40 mmol, 2.0 eq.) in THF (50 mL) was added methyl chloroformate (1.2 mL, 15.20 mmol, 1.2 eq.) at 0° C. The mixture was stirred at 0° C. for 10 min and filtered. To this filtrate was added a suspension of NaBH4 (0.97 g, 25.40 mmol, 2 eq.) in water (1.0 mL) at 0° C. The mixture was stirred at 0° C. for 1 h, quenched with NH4Cl(aq) solution, and extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give (3-chloropyrazin-2-yl)methanol (400 mg, 22percent) as a white solid. 1H NMR (400 MHz, MeOD) delta 8.58 (d, J=2.5 Hz, 1H), 8.38 (d, J=2.5 Hz, 1H), 4.84 (s, 2H). LRMS (M+H+) m/z 145.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With vanadium nitrate; In acetonitrile; at 40℃; for 10h;Green chemistry; | 1.44 g of 3-chloro-2-pyrazine methanol, 2 mol% of vanadium nitrate (relative to the substrate 3-chloro-2-pyrazine methanol),Add to the 50mL reaction tube, Add 5mL of acetonitrile,Fill the air ball, close the reaction tube, and raise the temperature to 40 C with stirring.And kept for 10 h, until the reaction is over, and cooled to room temperature.Sampling was analyzed using gas chromatography.The conversion rate of 3-chloro-2-pyrazine methanol is 96.1%.The selectivity of 3-chloro-2-pyrazinecarboxaldehyde is greater than 99%. |
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