Structure of 480424-70-2
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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. : | 480424-70-2 |
Formula : | C14H19BO4 |
M.W : | 262.11 |
SMILES Code : | CC(OC1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1)=O |
MDL No. : | MFCD03453060 |
InChI Key : | KHBAJCWEQNVCSN-UHFFFAOYSA-N |
Pubchem ID : | 2774004 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 74.42 |
TPSA ? Topological Polar Surface Area: Calculated from |
44.76 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 |
2.66 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.91 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.54 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.77 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.18 |
Solubility | 0.175 mg/ml ; 0.000666 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.25 |
Solubility | 0.147 mg/ml ; 0.00056 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.08 |
Solubility | 0.022 mg/ml ; 0.0000839 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) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.01 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 |
2.0 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) |
2.93 |
* 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 |
---|---|---|
52% | With water; potassium carbonate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In ethanol; toluene; at 60℃; for 3h;Inert atmosphere; | N-(3-((4-(3-bromophenoxy)benzyl)(4-cyanobenzyl)amino)-2-methylphenyl) methanesulfonamide (30 mg, 0.05 mmol), 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)phenyl acetate (20 mg, 0.08 mmol), S-Phos (2 mg, 0.01 mmol), palladium acetate(0.3 mg, 0.001 mmol) and potassium carbonate (14 mg, 0.1 mmol) were dissolved in 1 mL of toluene/EtOH/H2theta 100:10:1 solvent mixture. Reaction mixture was stirred at 6O0C under nitrogen atmosphere for 3 hours. Water was added and product extracted with DCM. Crude material was purified on a silica column (DCM/MeOH 99:1) and further purified by preparative HPLC (40 - 90 % MeOH/0.05 % HCOOH, pH2.8, 25 mL/min, 30 minute gradient time). Yield 16 mg (52%).IH (acetone-d6, 500MHz): 7.67 (m, 2H), 7.53 (m, 2H), 7.48 (m, 2H), 7.40 (t, IH, J=8.1Hz), 7.35 (m, IH), 7.32 (m, 2H), 7.19-7.16 (m, 2H), 7.08 (t, IH, J=8.2Hz), 7.03(dd, IH, J=8.1, 1.0Hz), 6.97 (m, 2H), 6.91 (m, 2H), 6.88 (m, IH), 4.25 (s, 2H9, 4.12 (s,2H), 2.93 (s, 3H9 and 2.53 (s, 3H);MS (ESI) mlz 590.3 (M + H), 588.3 (M - H). |
52% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; water; potassium carbonate;palladium diacetate; In ethanol; toluene; at 60℃; for 3h;Inert atmosphere; | N-(3-((4-(3-bromophenoxy)benzyl)(4-cyanobenzyl)amino)-2-methylphenyl)methanesulfonamide (30 mg, 0.05 mmol), <strong>[480424-70-2]4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl acetate</strong> (20 mg, 0.08 mmol), S-Phos (2 mg, 0.01 mmol), palladium acetate (0.3 mg, 0.001 mmol) and potassium carbonate (14 mg, 0.1 mmol) were dissolved in 1 mL of toluene/EtOH/H2O 100:10:1 solvent mixture. Reaction mixture was stirred at 60 C. under nitrogen atmosphere for 3 hours. Water was added and product extracted with DCM. Crude material was purified on a silica column (DCM/MeOH 99:1) and further purified by preparative HPLC (40-90% MeOH/0.05% HCOOH, pH2.8, 25 mL/min, 30 minute gradient time). Yield 16 mg (52%).1H (acetone-d6, 500 MHz): 7.67 (m, 2H), 7.53 (m, 2H), 7.48 (m, 2H), 7.40 (t, 1H, J=8.1 Hz), 7.35 (m, 1H), 7.32 (m, 2H), 7.19-7.16 (m, 2H), 7.08 (t, 1H, J=8.2 Hz), 7.03 (dd, 1H, J=8.1, 1.0 Hz), 6.97 (m, 2H), 6.91 (m, 2H), 6.88 (m, 1H), 4.25 (s, 2H9, 4.12 (s, 2H), 2.93 (s, 3H9 and 2.53 (s, 3H);MS (ESI) m/z 590.3 (M+H), 588.3 (M-H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate; In 1,2-dimethoxyethane; water; at 80℃; for 2.5h;Inert atmosphere; | A mixture of 8 (282 mg, 0.83 mmol), <strong>[480424-70-2]4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl acetate</strong> (260 mg, 0.99 mmol), Na2CO3 (261 mg, 2.46 mmol) and Pd(PPh3)2Cl2 (18 mg, 3 mol % Pd) in DME/water (8 mL, 3/1, v/v) was heated at 80 C for 2.5 h under N2 gas. The reaction mixture was poured into saturated aqueous NaHCO3 and extracted with ether. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification of the residue by silica gel column chromatography (EtOAc/n-hexane, 1/10, v/v) yielded 10 (193 mg, 59%) as a colorless crystal; mp, 123-124 C. 1H NMR (300 MHz, CDCl3): delta 1.43 (9H, s), 2.31 (3H, s), 2.77 (4H, br), 3.31 (4H, br), 7.01 (1H, d, J = 7.7 Hz), 7.06-7.16 (3H, m), 7.23-7.31 (2H, m), 7.63 (2H, d, J = 8.4 Hz). 13C NMR (75 MHz, CDCl3): delta 21.2, 28.4, 44.1 (br), 51.2, 79.7, 118.7, 121.3, 123.4, 128.6, 129.9, 131.5, 134.4, 138.3, 149.6, 149.7, 154.8, 169.5. FAB-MS: m/z 397 (M+H). |
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