Structure of 286961-15-7
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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. : | 286961-15-7 |
Formula : | C19H26BNO4 |
M.W : | 343.23 |
SMILES Code : | O=C(N1CCC(B2OC(C)(C)C(C)(C)O2)=CC1)OCC3=CC=CC=C3 |
MDL No. : | MFCD11521562 |
InChI Key : | QDSFHRPYZPQWEJ-UHFFFAOYSA-N |
Pubchem ID : | 11290836 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.53 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 101.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.0 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 |
2.85 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.84 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.95 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.61 |
Solubility | 0.084 mg/ml ; 0.000245 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.52 |
Solubility | 0.104 mg/ml ; 0.000304 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.53 |
Solubility | 0.0101 mg/ml ; 0.0000294 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) |
Yes |
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 |
-6.37 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) |
3.95 |
* 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 |
---|---|---|
100% | With triethylamine; In dichloromethane; at 20℃; for 2h; | Example 2: Tetrahydropyridine 2 was prepared in 3 steps starting with the deprotection of 1 using Method 3. The resulting HCl amine salt was dissolved in dichloromethane (0.2 M). Benzyl chloroformate (1.2 equiv) was added followed by triethylamine (3.0 equiv). The reaction was allowed to stir at room temperature for 2h after which point it was diluted with IN HCl and extracted with excess dichloromethane. The organic layer was dried over MgSpsi4 and concentrated to provide the desired carbamate in quantitative yield, which was converted directly to boronic acid 2 using Method 2. [M-H]- = 260.1 m/z. Activity: B |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate; In 1,4-dioxane; water; at 90℃; for 2.5h;Inert atmosphere; Sealed tube; | Aqueous sodium carbonate solution (2M) and 1,4-dioxane were both degassed by passing astream of nitrogen through a fritted glass tube into the liquids for 15 mm. Benzyl 4-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1 (2H)-carboxylate (250 mg, 0.73mmol), <strong>[34259-99-9]4-bromo-1,3-thiazole</strong> (119 mg, 0.73 mmol), [1,1?-Bis(diphenylphosphino)ferrocene]dichloropalladium(ll) (32 mg, 0.044 mmol), degassed aqueous sodium carbonate solution (2M, 1.1 mL, 2.2 mmol) and degassed 1,4-dioxane (3 mL) were placed into a nitrogen flushed tube, sealed and heated under pressure at 90 °C for 2.5 h. The cooled reaction mixture was diluted with H20 and extracted with EtOAc. The organic phasewas passed through a phase separator and concentrated onto flash silica (15 mL). The resulting powder was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 50 g, 40-63 jim, 60 A], 40 mL per mm, 65percent Et20 in isohexane isochratic) to give benzyl 4-(1 ,3-thiazol-4-yl)-3,6-dihydropyridine-1 (2H)-oarboxylate (173 mg, 79percent).LCMS (Method C): mlz 301 (M+H) (ES?), at 1.46 mi UV active. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; at 74℃;Inert atmosphere; | A reaction mixture of 6-iodo-1H-indazole (1 g, 4.10 mmcl), benzyl 4-(4,4,5,5-tetramethyl-1 ,3,2-diox-aborolan-2-yI)-5,6-dihydropyridine-1(2H)-carboxylate (1.41 g, 4.10 mmol),PdCI2(dppf)-CH2CI2 adduct (0.335 g, 0.410 mmol) and sodium carbonate (1.30 g, 12.3 mmol)was bubbled with nitrogen and stirred at 74 C (oil bath) overnight. Then the reactionmixture was filtered, concentrated to remove solvent and diluted with ethyl acetate (180 mL) and water (50 mL). Separated organic part was dried over anhydrous Na2504, fitered and concentrated. Purification via ISCO system (ethyl acetate/petroleum ether) afforded the title product.LC-MS (ESI) [mobile phase: from 95% water (0.05% TFA) and 5% CH3CN to 5% water (0.05%TFA) and 95% CH3CN in 5.0 mm]: m/z 334 [M + H] Rt 3.50 mm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,2-dimethoxyethane; water; at 120.0℃; for 0.75h;Sealed tube; Inert atmosphere; Microwave irradiation; | General procedure: The boronic acid pinacol ester (1 equiv.), aryl halide (1 equiv.) and Pd(dppf)Cl2·CH2Cl2 adduct (0.1 equiv.) were dissolved in a mixture of DME and aqueous sodium carbonate (1M) in a microwave vial. The vial was sealed, evacuated and backfilled with N2. The reaction mixture was heated in the microwave at 120C for 45min and monitored by LCMS. The reaction mixture was concentrated in vacuo to give the crude material which was purified by Biotage column chromatography (see individual compounds for details of the eluent used). |
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