Structure of 1454682-74-6
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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. : | 1454682-74-6 |
Formula : | C20H32BFN2O3 |
M.W : | 378.29 |
SMILES Code : | O=C(NC1=CC(B2OC(C)(C)C(C)(C)O2)=C(C)C=C1F)NCCC(C)(C)C |
MDL No. : | MFCD30183445 |
InChI Key : | BFNHXYBUOCXLSH-UHFFFAOYSA-N |
Pubchem ID : | 89809537 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 27 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.65 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 109.12 |
TPSA ? Topological Polar Surface Area: Calculated from |
59.59 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.22 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.94 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.3 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.98 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.7 |
Solubility | 0.00759 mg/ml ; 0.0000201 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.43 |
Solubility | 0.0014 mg/ml ; 0.00000371 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-6.67 |
Solubility | 0.00008 mg/ml ; 0.000000211 mol/l |
Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.44 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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.77 |
* 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 |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In 1,4-dioxane; water; at 50.0℃;Inert atmosphere; | Combine l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)phenyl)urea (25.9 g, 68.5 mmol), 7-methyl-2-(methylamino)pyrido[2,3- d]pyrimidin-6-yl trifluoromethanesulfonate (22.09 g, 68.5 mmol), and NaHC03 (17.28 g, 206 mmol) in 1,4-dioxane (500 mL) and water (125 mL) and sparge with argon for 20 minutes. Add tetrakis(triphenylphosphine)palladium (3.96 g, 3.43 mmol) and then heat under argon at 50 C. Add additional portion of 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (300 mg, 0.55 mmol) and continue heating at 50 C overnight. Cool the mixture to RT, collect the solid by filtration, and wash with water then diethyl ether. Treat the solid with acetonitrile (50 mL) and heat the slurry at 80 C for 30 minutes. Collect the solid by filtration, wash with acetonitrile and dry under vacuum at 80 C to obtain a pale yellow solid. Treat the solid with MeOH (50 mL), and heat the mixture at 80 C for 1 hour. Cool to RT, collect the solid via filtration, wash with MeOH (20 mL), and dry under vacuum to obtain the title compound (22.5 g, 77% yield) as a pale yellow solid. MS (m/z): 425.2 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 85.0℃;Inert atmosphere; | Method B: Sparge a suspension of l-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)urea (4.48 g, 11.8 mmol), 6-bromo-N,7- dimethylpyrido[2,3-d]pyrimidin-2-amine (3.0 g, 11.8 mmol) and K2CO3 (4.91 g, 35.6 mmol) in dioxane (80 mL) and water (20 mL) with argon, treat with tetrakis(triphenylphosphine)palladium (0.685 g, 0.593 mmol) and heat at 85 C overnight. Remove the dioxane under reduced pressure, treat the mixture with EtOAc and brine, separate the layers, dry the organics over Na2S04, concentrate and purify by silica gel chromatography (40% to 100% EtOAc/hexane, 100% EtOAc, 5% MeOH/ EtOAc). Treat the material with CH3CN, heat at 80C for 1 hour, cool to RT and collect the solid via filtration to afford the title compound (3.52 g, 70%> yield) as a pale yellow solid. MS (m z): 425.2 (M+l). |
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