Structure of 33252-29-8
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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. : | 33252-29-8 |
Formula : | C6H3ClN2 |
M.W : | 138.55 |
SMILES Code : | N#CC1=NC(Cl)=CC=C1 |
MDL No. : | MFCD00274527 |
InChI Key : | PGZHSVWXFKKCNR-UHFFFAOYSA-N |
Pubchem ID : | 118424 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 9 |
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 | 33.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.68 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.46 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.61 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.4 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.46 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.37 |
Solubility | 0.59 mg/ml ; 0.00426 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.26 |
Solubility | 0.758 mg/ml ; 0.00547 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.7 |
Solubility | 0.278 mg/ml ; 0.002 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 |
-5.82 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) |
1.75 |
* 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 |
---|---|---|
With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 70℃; | To a solution of <strong>[1196473-37-6]3H-benzo[c][1,2]oxaborole-1,6-diol</strong> (2.0 g, 13.33 mmol) in anhydrous DMF (8 mL) were added Cs2CO3 (10.86 g, 33.33 mmol) and 6-chloro-pyridine-2-carbonitrile (1.71 g, 14.0 mmol) at room temperature. After stirring at 70° C. for 8 h, the reaction mixture was cooled to 0° C. diluted with water (20 mL) and acidified to pH 3 using diluted hydrochloric acid. The mixture was extracted with EtOAc. The extract was washed with brine and dried to give the crude product which was purified by chromatography on silica gel (DCM/MeOH=40:2) to give 2.20 g of product. 1HNMR (400 MHz, DMSO-d6) delta 9.23 (br. s., 1H), 8.08 (m, 1H), 7.78 (d, J=7.33 Hz, 1H), 7.35-7.56 (m, 3H), 7.29 (dd, J=8.20, 2.05 Hz, 1H), 5.01 (s, 2H). MS (ESI) m/z=251 [M-H]-. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87.0% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; at 100℃;Inert atmosphere; | The title compound of this step is prepared by the method described in the first step of Example 1,That is, 2-(4-Boc-piperazin-1-yl)pyrimidine-5-boronic acid pinacol ester (2.70 g, 6.93 mmol),6-chloropyridine-2-carbonitrile (0.80 g, 5.77 mmol), tricyclohexylphosphine (0.16 g, 0.58 mmol),Tris(dibenzylideneacetone)palladium(0) (0.17 g, 0.29 mmol) and potassium phosphate (2.50 g, 11.55 mmol) atA mixed solvent of 1,4-dioxane (20 mL) and water (2 mL) was prepared by reacting at 100 C overnight under a nitrogen atmosphere.The obtained crude product was isolated and purified by column chromatography (dichloromethane:methanol (V:V)=40:1) to give the title compound(Yellow solid, 1.84 g, 87.0%). |
87% | With tris-(dibenzylideneacetone)dipalladium(0); tricyclohexylphosphine; In 1,4-dioxane; water; at 100℃;Inert atmosphere; | The title compound of this step was prepared by the method described in Example 1, Step 1, namely, <strong>[940284-98-0]2-[4-(Boc)piperazin-1-yl]pyrimidine-5-boronic acid pinacol ester</strong> (2.70 g, 6.93 mmol), 6-chloropyridine-2-nitrile (0.80 g, 5.77 mmol), tricyclohexylphosphine (0.16 g, 0.58 mmol), tris(dibenzylideneacetone)palladium(0) (0.17 g, 0.29 mmol) and potassium phosphate (2.50 g, 11.55 mmol) were added to a mixture of 1,4-dioxane (20 mL) and water (2 mL). The reaction was heated to 100 C overnight under N2. The crude product was purified by column chromatography (dichloromethane/methanol (v/v) = 40/1) to give the title compound as a yellow solid (1.84 g, 87.0%).MS (ESI, pos. ion) m/z: 311.40 [M+H-56]?HNIVIR (400 1?IFlz, CDC13) (ppm): 8.97 (s, 2H), 7.907.83 (m, 1H), 7.80 (dd, J 8.1,0.9 Hz, 1H), 7.58 (dd, J= 7.4, 0.9 Hz, 1H), 3.973.86 (m, 4H), 3.583.46 (m, 4H), 1.51 (s, 9H). |
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