Structure of 330794-35-9
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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.
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CAS No. : | 330794-35-9 |
Formula : | C18H28BNO4 |
M.W : | 333.23 |
SMILES Code : | CC(C)(C)OC(=O)NCC1=CC=C(C=C1)B1OC(C)(C)C(C)(C)O1 |
MDL No. : | MFCD06409942 |
InChI Key : | CUDCEJRRWNIPDL-UHFFFAOYSA-N |
Pubchem ID : | 3415442 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 24 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.61 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 96.43 |
TPSA ? Topological Polar Surface Area: Calculated from |
56.79 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 |
3.41 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.86 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.83 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.84 |
Solubility | 0.0478 mg/ml ; 0.000143 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.28 |
Solubility | 0.0174 mg/ml ; 0.0000522 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.32 |
Solubility | 0.00158 mg/ml ; 0.00000474 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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.91 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) |
3.22 |
* 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 |
---|---|---|
75% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In diethylene glycol dimethyl ether; water; at 85℃; for 8h;Inert atmosphere; | Under the protection of argon, compound (f) was added sequentially in a 50 mL two-necked bottle.(400 mg, 1.2 mmol), K2CO3 (220 mg, 1.6 mmol),Compound (d) (273 mg, 0.4 mmol) and Pd(PPh3) 4 (46 mg, 0.04 mmol),Add 25 mL of ethylene glycol dimethyl ether and water mixed solvent (4:1 by volume).The mixture was reacted at 85 C for 8 hours.After completion of the reaction, the mixture was cooled to room temperature, and the solvent was evaporated under reduced pressure.10 mL of water was added to the reaction mixture, and the mixture was extracted with dichloromethane.The organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure.Separation by column chromatography, eluent: dichloromethane (DCM) / methanol (MeOH) = (300:1),A dark brown solid (280 mg, 75%) was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; at 100℃;Inert atmosphere; | A 100 mL round bottom flask is charged with 4-bromobenzo[cl[1,2,Slthiadiazole (1.61 g, 7.49 mmol, 1.00 equiv), tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)carbamate (2.74 g, 8.24 mmol, 1.10 equiv), potassium carbonate (3.10 g, 22.5 mmol, 3.00 equiv), and [1,1? -Bis(diphenylphosphino)ferrocenel dichloropalladium(ll) (0.274 g, 0.374 mmol, 5.00 molpercent). The flask is connected to a reflux condenser and is placed under a nitrogen atmosphere. 38 mL of nitrogen-sparged 9:1 dioxane:water is added and the mixture was stirred at 100°C overnight.The solution is cooled and quenched with water. Product is extracted with several portions of dichloromethane. Combined organic fractions are dried with Mg504, concentrated, and purified by chromatography on silica gel (20percent EtOAc in hexane). A white solid is isolated. The material is immediately dissolved in 30 mL dichloromethane and 3 mL concentrated HC1 are added. The mixture is stirred at ambient temperature overnight. The slurry is filtered, and the isolated white solid is rinsed with a few additional portions of dichloromethane. The solid is dried in a vacuum oven for several hours. Proton/CarbonNMR are consistent with the HC1-salt of the desired product. ?H NMR (500 MHz, DMSOd 6) oe 8.62 (s, 3H), 8.11 (dd, J= 8.7, 1.1 Hz, 1H), 8.06?7.96 (m, 2H), 7.88 (dd, J=7.0, 1.1 Hz, 1H), 7.82 (dd, J= 8.6, 7.0 Hz, 1H), 7.68 (d, J= 8.1 Hz, 2H), 4.11 (s, 2H). ?3C NMR (126 MHz, DMSO-d6) oe 154.95, 152.61, 136.77, 134.14, 132.71, 130.08, 129.16, 129.07, 128.01, 120.61, 41.81. | |
A 100 mL round bottom flask is charged with 4-bromobenzo[c][l,2,5]thiadiazole (1.61 g, 7.49 mmol, 1.00 equiv), tert-butyl (4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)benzyl)carbamate (2.74 g, 8.24 mmol, 1.10 equiv), potassium carbonate (3.10 g, 22.5 mmol, 3.00 equiv), and [l,l'-bis(diphenylphosphino)ferrocene] dichloropalladium(II) (0.274 g, 0.374 mmol, 5.00 molpercent). The flask is connected to a reflux condenser and is placed under a nitrogen atmosphere. 38 mL of nitrogen-sparged 9:1 dioxane:water is added and the mixture was stirred at 100°C overnight. The solution is cooled and quenched with water. Product is extracted with several portions of dichloromethane. Combined organic fractions are dried with MgSO4, concentrated, and purified by chromatography on silica gel (20percent EtOAc in hexane). A white solid is isolated. The material is immediately dissolved in 30 mL dichloromethane and 3 mL concentrated HC1 are added. The mixture is stirred at ambient temperature overnight. The slurry is filtered, and the isolated white solid is rinsed with a few additional portions of dichloromethane. The solid is dried in a vacuum oven for several hours. Proton/Carbon NMR are consistent with the HCl-salt of the desired product. NMR (500 MHz, DMSO- d6) delta 8.62 (s, 3H), 8.11 (dd, / = 8.7, 1.1 Hz, 1H), 8.06 - 7.96 (m, 2H), 7.88 (dd, 7 = 7.0, 1.1 Hz, 1H), 7.82 (dd, / = 8.6, 7.0 Hz, 1H), 7.68 (d, / = 8.1 Hz, 2H), 4.11 (s, 2H). 13C NMR (126 MHz, DMSO-ifc) delta 154.95, 152.61, 136.77, 134.14, 132.71, 130.08, 129.16, 129.07, 128.01, 120.61, 41.81. |
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