Structure of 36070-83-4
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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. : | 36070-83-4 |
Formula : | C7H7BrN2O2 |
M.W : | 231.05 |
SMILES Code : | BrC1=CN=C(C=N1)C(=O)OCC |
MDL No. : | MFCD11044905 |
InChI Key : | YMWDNHSAHXMMHH-UHFFFAOYSA-N |
Pubchem ID : | 19962215 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.08 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.61 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.3 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.26 |
Solubility | 1.26 mg/ml ; 0.00545 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.99 |
Solubility | 2.34 mg/ml ; 0.0101 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.99 |
Solubility | 0.235 mg/ml ; 0.00102 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) |
Yes |
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 |
-6.79 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 |
0.0 |
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) |
2.23 |
* 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 |
---|---|---|
8%; 9% | With copper; trifluoroacetic acid; In N,N-dimethyl-formamide; at 50.0℃; for 2.0h; | To a mixture of copper powder (286 mg, 4.50 mmol) and DMF (3.5 mL) was added TFA (11 mu, 0.15 mmol), and the resulting mixture was stirred at room temperature for 30 min. To the mixture were added <strong>[36070-83-4]ethyl 5-bromopyrazine-2-carboxylate</strong> (VII, 347 mg, 1.50 mmol) and ethyl bromodifluoroacetate (289 mu, 2.25 mmol), and the mixture was stirred at 50 C for 2 h. To the reaction mixture were added a saturated aqueous sodium bicarbonate solution (10 mL) and ethyl acetate (15 mL), and the organic layer was separated. The organic layers was washed twice with an aqueous sodium chloride solution (5%, 20 mL each). After the organic layer was dried over sodium sulfate, concentration at 40 C under reduced pressure and purification of the residue by silica gel chromatography (ethyl acetate and ft-hexane) afforded the title compound (VIII, 30.9 mg, 8% yield and IX, 34.9 mg, 9% yield). [0052] The data of NMR for the title compound (IX) is as follows. [5-(ethoxycarbonyl)pyrazin-2-yl](difluoro)acetic acid (IX) NMR (400 MHz, CDC13) delta: 1.49 (t, J- 6.8 Hz, 3H), 4.55 (q, J = 6.8 Hz, 2H), 9.40 (s, 1H), 9.76 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.5% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 80.0℃; for 8.0h;Inert atmosphere; | Embodiment 66 ethyl 5-((4,4-dimethylthiochroman-6-yl)ethynyl)pyrazin-2-carboxylate ethyl 5-bromopyridazin-2-carboxylate (600mg, 2.61mmol) and 6-ethynyl-4,4-dimethylbenzothiopyran (635mg, 3.13mmol) were added to a flask, followed by addition of Pd(PPh3)2Cl2 (66mg, 0.094mmol) and CuI (36mg, 0.188mmol). After the flask was purged with argon for 3 times to remove oxygen, 6mL dry DMF and 0.4mL dry Et3N were added via syringe. Then the reaction was continued at 80C for 8 h and monitored by TLC. After completion of the reaction, the reaction was quenched with saturated ammonium chloride solution. The mixture was diluted with ethyl acetate, washed with saturated ammonium chloride solution and saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered, concentrated and purified by flash column chromatography (PE:EtOAc = 50:1) to give WYC-322 (656mg, 71.5%). 1H NMR (500 MHz, CDCl3) delta 9.20 (d, J = 1.4 Hz, 1H), 8.76 (d, J = 1.4 Hz, 1H), 7.58 (d, J = 1.7 Hz, 1H), 7.23 (dd, J = 8.2, 1.8 Hz, 1H), 7.04 (d, J = 8.2 Hz, 1H), 4.46 (q, J = 7.1 Hz, 2H), 3.02 - 2.97 (m, 2H), 1.92 - 1.87 (m, 2H), 1.41 (t, J = 7.1 Hz, 3H), 1.29 (s, 6H). 13C NMR (126 MHz,CDCl3) delta 163.65, 146.68, 145.70, 143.08, 142.31, 140.30, 136.14, 130.54, 129.51, 126.74, 116.00, 97.55, 85.68, 62.37, 36.91, 32.99, 29.89, 23.27, 14.31. ESI(+)-MS: 353.5 [M+1]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With sulfuric acid; for 6.0h;Inert atmosphere; Reflux; | Embodiment 63 ethyl 5-bromopyridazin-2-carboxylate 5-Bromopyridazin-2-carboxylic acid (1.0g, 5mmol) was added to a flask, followed by addition of 5mL anhydrous ethanol under argon atmosphere. The mixture was cooled to 0C under an ice bath, then 0.3mL concentrated sulfuric acid was added dropwise. After completion of the dropwise addition, the reaction solution was heated to reflux and stirred for 6 h, meanwhile TLC was used to monitor the reaction. After completion of the reaction, the reaction solution was cooled to room temperature, treated with 1mol/L sodium hydroxide to neutralize sulfuric acid to make a neutral solution, then washed with saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered, dried, and purified by flash column chromatography (PE:EtOAc = 50:1) to give ethyl 5-bromopyridazin-2-carboxylate (0.42g, 37%). 1H NMR (500 MHz, CDCl3) delta 9.01 (d, J = 1.3 Hz, 1H), 8.76 (d, J = 1.3 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCl3) delta 163.39, 147.30, 146.31, 144.65, 141.89, 62.67, 14.30. ESI(+)-MS: 231.2 [M+1]+. |
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