Structure of 1171892-42-4
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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. : | 1171892-42-4 |
Formula : | C14H22BNO3 |
M.W : | 263.14 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CN=CC(OC(C)C)=C2)O1 |
MDL No. : | MFCD13182246 |
InChI Key : | DPMKLRJKZXEWSN-UHFFFAOYSA-N |
Pubchem ID : | 59612998 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.64 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 76.82 |
TPSA ? Topological Polar Surface Area: Calculated from |
40.58 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 |
2.61 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.17 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.82 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.89 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.15 |
Solubility | 0.186 mg/ml ; 0.000706 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.11 |
Solubility | 0.203 mg/ml ; 0.000773 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.19 |
Solubility | 0.017 mg/ml ; 0.0000646 mol/l |
Class? Solubility class: Log S scale |
Moderately 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 |
-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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.3 |
* 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 potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In acetonitrile; at 160℃; for 0.25h;Inert atmosphere; Biotage "Initiator" microwave; | Intermediate 70:3-[(1-methylethyl)oxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineA mixture of 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (705mg, 2.78mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(ii)dichloride dichloromethane complex (76mg, 0.093mmol), potassium acetate (681 mg, 6.94mmol) was sealed in a microwave vial and placed under nitrogen via a needle through the septum and applying alternately vacuum and nitrogen. A solution of 3-bromo-5-[(1-methylethyl)oxy]pyridine (500mg, 2.314mmol) in anhydrous acetonitrile (1OmL) was added, the solution degassed by alternate application of vacuum and nitrogen. The reaction mixture was then heated in a Biotage "Initiator" microwave at 16O0C for 15 minutes. After cooling, the reaction was filtered and the filtrate evaporated to dryness to give the crude (approximately 60% pure by NMR analysis) title compound (960mg, >; 100% yield) which was used subsequently without further purification. LCMS (Method A): Rt 0.65 minutes; m/z 182 (ionizes as the boronic acid). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4% | With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 130℃; for 0.5h;Biotage "Initiator" microwave; | Example 157: trans-4-({4-[(6-{5-[(1-methylethyl)oxy]-3-pyridinyl}-1,3-benzothiazol-2-yl)amino]-2-pyrimidinyl}amino)cyclohexanolA mixture of <strong>[1171892-42-4]3-[(1-methylethyl)oxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine</strong> (125mg, 0.476mmol), trans-4-({4-[(6-bromo-1,3-benzothiazol-2-yl)amino]-2-pyrimidinyl}amino)cyclohexanol (100mg, 0.238mmol), tetrakis(triphenylphosphine)-palladium(O) (82mg, 0.071 mmol), caesium carbonate (233mg, 0.714mmol) in 1,4-dioxane (2mL) and water (0.5mL) was sealed and heated in a Biotage "Initiator" microwave at 1300C for 30 minutes. The cooled reaction mixture was evaporated to dryness and the product was purified by mass-directed automated preparative HPLC (ammonium bicarbonate modifier) followed by ion exchange chromatography using an SCX (sulfonic acid) solid-phase extraction cartridge and eluting with methanol followed by 2M ammonia in methanol to afford the title compound (4.8mg, 4% yield). LCMS (Method B): Rt 2.48 minutes; m/z 477 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
18% | With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 130℃; for 0.5h;Biotage "Initiator" microwave; | Example 196: trans-4-[4-[(6-{5-[(1-methylethyl)oxy]-3-pyridinyl}-1 ,3-benzothiazol-2-yl)amino]-6-(4-morpholinylmethyl)-2-pyrimidinyl]amino}cyclohexanolA mixture of <strong>[1171892-42-4]3-[(1-methylethyl)oxy]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine</strong> (101 mg, 0.385mmol), trans-4-[4-[(6-bromo-1,3-benzothiazol-2-yl)amino]-6-(4-morpholinylmethyl)-2-pyrimidinyl]amino}cyclohexanol (100mg, 0.193mmol), tetrakis(triphenylphosphine)palladium(0) (66.7mg, 0.058mmol), caesium carbonate (188mg, 0.578mmol) in 1 ,4-dioxane (2mL) and water (0.5ml_) was sealed and heated in a Biotage "Initiator" microwave at 1300C for 30 minutes. The cooled reaction mixture was evaporated to dryness. The product was purified by mass-directed automated preparative HPLC (formic acid modifier) to afford the title compound (20mg, 0.035mmol, 18% yield). LCMS (Method A): Rt 0.71 minutes; m/z 576 (MH+). |
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