Structure of 330793-01-6
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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. : | 330793-01-6 |
Formula : | C17H26BNO4 |
M.W : | 319.20 |
SMILES Code : | CC(C)(C)OC(=O)NC1=CC=C(C=C1)B1OC(C)(C)C(C)(C)O1 |
MDL No. : | MFCD02179439 |
InChI Key : | HSJNIOYPTSKQBD-UHFFFAOYSA-N |
Pubchem ID : | 2734617 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 23 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.59 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 93.16 |
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 |
3.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.14 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.86 |
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 |
2.06 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.87 |
Solubility | 0.0432 mg/ml ; 0.000135 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.34 |
Solubility | 0.0144 mg/ml ; 0.0000452 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.93 |
Solubility | 0.00378 mg/ml ; 0.0000118 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 |
-5.78 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) |
3.39 |
* 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 |
---|---|---|
36% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 110℃; for 12h;Inert atmosphere; | A mixture of bis(pinacolato)diboron (10.5 g, 41.5 mmol), 4 (7.75 g, 28.5 mmol), Pd(dppf)Cl2 (0.79 g, 1.1 mmol) and potassium acetate (7.0 g, 71.4 mmol) in dry dioxane (100 mL) was added into a 250 mL round bottom flask. The mixture was stirred for 12 h at 110 C under the protection of argon. After being cooled to room temperature, it was filtered and the filtrate was concentrated on a rotary evaporator. The residue was subjected to column chromatography over silica gel (PE/EA 10:1) to give 5 (3.26 g, 36%) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta 9.53(s, 1H), 7.56(d, J = 8.5 Hz, 2H), 7.47(d, J = 8.5 Hz, 2H), 1.48(s, 9H), 1.29(s, 12H). |
With potassium acetate; In n-heptane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide; | b tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate A mixture of tert-butyl N-[(4-bromophenyl)carbamate (5.95 g, 0.0219 mol), diboron pinacol ester (6.67 g, 0.0263 mol), [1.1'-bis(diphenylphosphino)ferrocene]-dichloropalladium (II) complex with dichloromethane (1:1) (0.536 g, 0.00066 mol) and potassium acetate (6.47 g, 0.066 mol) in N,N-dimethylformamide (120 mL) was heated at 80 C. under an atmosphere of nitrogen for 16 hours. The mixture was allowed to cool to ambient temperature and the solvent removed under reduced pressure. Dichloromethane (100 mL) was added to the residue and the resulting solid was removed by filtration through a pad of Celite. The filtrate was concentrated to leave a yellow oil which was purified by flash chromatography on silica using ethyl acetate/n-heptane (7:93) as mobile phase. The resulting fractions were concentrated, the residue was triturated in n-heptane and the precipitate collected by filtration to yield tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (6.0 g, 0.0188 mol) as a white solid. 1H NMR (DMSO-d6, 400 MHz) delta 9.50(s, 1H), 7.55 (d, 2H), 7.46 (d, 2H), 1.47 (s, 9H), 1.27 (s, 12H). | |
With potassium acetate; In n-heptane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide; | b) tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate A mixture of tert-butyl N-[(4-bromophenyl)carbamate (5.95 g, 0.0219 mol), diboron pinacol ester (6.67 g, 0.0263 mol), [1.1'-bis(diphenylphosphino)ferrocene]-dichloropalladium (II) complex with dichloromethane (1:1) (0.536 g, 0.00066 mol) and potassium acetate (6.47 g, 0.066 mol) in N,N-dimethylformamide (120 mL) was heated at 80 C. under an atmosphere of nitrogen for 16 hours. The mixture was allowed to cool to ambient temperature and the solvent removed under reduced pressure. Dichloromethane (100 mL) was added to the residue and the resulting solid was removed by filtration through a pad of Celite. The filtrate was concentrated to leave a yellow oil which was purified by flash chromatography on silica using ethyl acetate/n-heptane (7:93) as mobile phase. The resulting fractions were concentrated, the residue was triturated in n-heptane and the precipitate collected by filtration to yield tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (6.0 g, 0.0188 mol) as a white solid. 1H NMR (DMSO-d6, 400 MHz) delta 9.50(s, 1H), 7.55 (d, 2H), 7.46 (d, 2H), 1.47 (s, 9H), 1.27 (s, 12H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 110℃; for 12h; | General procedure: Palladium tetraphenylphosphine (115mg, 0.10mmol) and potassium carbonate solution (2M, 100muL) were added to a solution of 4-bromo-2-nitrophenol (150mg, 0.69mmol) and boronic ester (300mg, 0.82mmol) in dioxane (40mL) and the mixture was refluxed at 110°C for 12h. After 12h, the reaction mixture was concentrated to dryness and the residue so obtained was purified via column chromatography (SiO2, 100:1, CH2Cl2: acetone) to afford desired product as a yellow amorphous solid (136mg, 60percent). |
72% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; at 110℃; for 12h;Reflux; | tert-butyl (4'-hydroxy-2'-nitro-[1,1'-biphenyl]-4-yl)carbamate (32b): Palladium tetraphenylphosphine (0.10 mmol) and potassium carbonate solution (2M, 100 muL) were added to a solution of phenol (30b, 0.69 mmol) and boronic ester (0.82 mmol) in dioxane (10 mL) and the mixture was refluxed at 110 oC for 12 hours. After 12 hours, the reaction mixture was concentrated to dryness and the residue so obtained was purified via column chromatography (SiO2, 100:1, CH2Cl2:acetone) to afford desired product as a yellow amorphous solid (210 mg, 72percent). 1H NMR (500 MHz, chloroform-d) delta 7.40 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 2.6 Hz, 1H), 7.28 (d, J = 5.0 Hz, 1H), 7.23? 7.17 (m, 2H), 7.07 (dd, J = 8.4, 2.6 Hz, 1H), 6.53 (s, 1H), 5.47 (s, 1H), 1.54 (s, 9H).13C NMR (126 MHz, CDCl3) delta 155.35, 153.00, 149.83, 138.39, 133.34, 132.05, 129.00, 128.64, 119.86, 118.99, 111.40, 81.16, 28.64. HRMS (ESI-) m/z [M-H+] calcd for C17H18N2O5 329.1137, found 329.1132 |
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