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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
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Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 405224-23-9
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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.
4.5
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CAS No. : | 405224-23-9 |
Formula : | C6H2BrClN2 |
M.W : | 217.45 |
SMILES Code : | N#CC1=C(Cl)N=CC(Br)=C1 |
MDL No. : | MFCD09801046 |
InChI Key : | MQOHJAYYYVQBSH-UHFFFAOYSA-N |
Pubchem ID : | 21948269 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H315-H318-H335 |
Precautionary Statements: | P280-P301+P310+P330-P302+P352-P305+P351+P338+P310 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 41.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.7 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.37 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.16 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.65 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.02 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.03 |
Solubility | 0.203 mg/ml ; 0.000932 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.63 |
Solubility | 0.515 mg/ml ; 0.00237 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.59 |
Solubility | 0.0564 mg/ml ; 0.000259 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 |
-6.05 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 |
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) |
1.89 |
* 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 |
---|---|---|
84% | With phosphorus pentachloride; In trichlorophosphate;Reflux; | 5-Bromo-2-chloronicotinonitrile (13) Compound 12 (69 mg, 0.35 mmol) and PCl5(109 mg, 0.52 mmol) were refluxed in POCl3 (5 mL) overnight. Themixture was cooled to room temperature and added to ice water in drops slowly,basified with NaOH (4 M)to pH 8, and extracted with CH2Cl2 (3×30 mL). Thecombined extracts were washed with aqueous NaHCO3, brine, dried overanhydrous Na2SO4, and concentrated in vacuum.Purification by chromatography (PE/EA = 20:1) provided compound 13 (63 mg, 84percent) as a yellow solid. MP:138~139°C. 1H NMR (400 MHz, CDCl3): delta 8.66 (d, J = 2.4 Hz, 1H), 8.12 (d, J = 2.4 Hz,1H).6 |
With phosphorus pentachloride; trichlorophosphate; for 3.0h;Heating / reflux; | 5-Bromo-2-chloro-nicotinonitrile 5-Bromo-2-oxo-1,2 dihydro-pyridine-3-carbonitrile (33 g, 166 mmol) was added to a suspension of PCl5 (96.6 g, 464 mmol) in POCl3 (20 ml, 216 mmol). The mixture was stirred at reflux for 3 hours, cooled to room temperature and then poured slowly into ice/water. The resulting solid was fitered, washed with water, and dried in vacuo to afford the title compounid. 1H NMR delta (d6 DMSO) 8.7 (d, 1H), 8.1 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With hydrogenchloride; sodium nitrite; In water; at -5 - 20℃; | To a stirred solution of compound 2 (4.6 g) in HC1 (48.4 mL ) was added sodium nitrite ( 5.3 mL ) dropwise at-5 C. The reaction mixture was stirred at room temperature for 2h. The resulting solids were collected by filtration and dried in vacuum to give compound 3 (4.4 g, 88%). |
88% | With hydrogenchloride; sodium nitrite; In water; at -5 - 20℃; for 2h; | Step-2 [0069] To a stirred solution of compound 2 (4.6 g) in HCl (48.4 mL) was added sodium nitrite (5.3 mL) dropwise at -5 C. The reaction mixture was stirred at room temperature for 2 h. The resulting solids were collected by filtration and dried in vacuum to give compound 3 (4.4 g, 88%). |
70% | With hydrogenchloride; sodium nitrite; In water; at 0℃; | Example 2; 5-bromo-2-chloropyridine-3-carbonitrile (3) ; [00141] Compound 2 was dissolved in cone. HCl at O2C, to which 1.1 equivalent of NaNO2 in H2O was added dropwise. Precipitation was formed. The white solid was filtered off, which gave the title compound 3. Overall yield was 70%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | With potassium tert-butylate; In tetrahydrofuran; at 90℃; for 0.25h;Microwave irradiation; | Method 64 [00589] 2-(azetidin-3-yloxy)-5-[2-([4-[4-(oxetan-3-yl)piperazin-l- yl]phenyl]amino)pyrimidin-4-yl]benzonitrile : To a solution of 5-bromo-2-chloropyridine-3- carbonitrile (950 mg, 4.37 mmol) in THF (15 mL) was added tert-butyl 3,3-difluoro-4- hydroxypiperidine-l-carboxylate (1250 mg, 5.27 mmol), and t-BuOK (1230 mg, 10.97 mmol) at room temperature. The reaction mixture was irradiated with microwave for 15 min at 90 C. When the reaction was done, the solids were filtered out and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography eluting with EtOAc in hexane (0% to 10% gradient) to yield tert-butyl 4-[(5-bromo-3-cyanopyridin-2-yl)oxy]-3,3- difluoropiperidine- l-carboxylate as a light yellow oil (725 mg, 39%). MS: m/z = 440.0 [M+H]+. |
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