Structure of 168759-60-2
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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. : | 168759-60-2 |
Formula : | C9H5BrO2 |
M.W : | 225.04 |
SMILES Code : | O=C1C=COC2=C1C=CC(Br)=C2 |
MDL No. : | MFCD12196350 |
InChI Key : | WWAOCYNUAWVKGQ-UHFFFAOYSA-N |
Pubchem ID : | 18686752 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 50.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.21 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.15 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.49 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.56 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.42 |
Solubility | 0.0854 mg/ml ; 0.00038 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.77 |
Solubility | 0.383 mg/ml ; 0.0017 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.47 |
Solubility | 0.00761 mg/ml ; 0.0000338 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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
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 |
-5.9 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 |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.72 |
* 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 |
---|---|---|
78% | A solution of diisobutylaluminum hydride in heptane (1.0 M, 60 mL, 60.0 mmol) was added dropwise to a solution of 7-bromo-4H-chromen-4-one (4.5 g, 20.0 mmol) in tetrahydrofuran at -78 C under an atmosphere of argon over a period of 30 minutes. After 30 minutes the reaction was quenched with a mixture of silica gel (10 g), and water (10 mL). The mixture was allowed to warm to room temperature and was filter through celite and the tetrahydrofuran was removed under reduced pressure. The residue was taken up in chloroform (100 mL) and washed with sodium hydroxide (IN, 25 mL) and dried over sodium sulfate. The mixture was filtered and the solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluant of dichloromethane. The product containing fractions were combined and the solvent was removed under reduced pressure to provide 7- bromochroman-4-one (3.57 g, 15.7 mmol, 78 %). | |
69% | Intermediate 5; 7-Bromo-2,3-dhydro-4W-chromen-4-one.;The solution of 7-Bromo-4H-chromen-4-one (26.0 g, 116 mmol) in absolute THF (500 mL) was stirred under argon for 1 h and then it was cooled to -80 0C. To a suspension formed a solution of diisobutylaluminum hydride 1M In heptane (173 mL, 173 mmol) was added during 30 minutes and the resulting mixture was stirred at -80 0C for additional 30 minutes. The solution was quenched by mixture of SiO2 (52 g) and H2O (52 mL), allowed to warm to 00C. Then SiO2 was filtered, washed with EtOAc and the solution was evaporated to dryness. The residue was dissolved in CHCI3 (400 mL), washed with 1 N NaOH (300 mL), dried over Na2SO4 and evaporated. The resulting solid was purified by column chromatography on SiO2 (63-100 mum, 1200 mL) in CHCI3 (80 - 100%) gradient in hexane to afford 101865-076 (18.1 g, 69%) as a pale yellow solid. LC/MS data: 226.9 V(M+Hf (Calculated for C8H7BrO2 227.06) (calc. monoisotopic mass is 225.96, calc. monoisotopic mass (M+Hf = 226.96). 1H NMR data (DMSO-d6): 7.66 (d, 1H1 J=8.3 Hz, Ar-H), 7.33 (d, 1H, J=2.0 Hz, Ar-H), 7.25 (dd, 1H, ^=8.3 Hz1 J2=L 7 Hz, Ar-H), 4.56 (t 2H, CH2 , J=6.6 Hz)1 2.80 (t, 2H, CH2 , J=S,6 Hz). | |
51.7% | With diisobutylaluminium hydride; In tetrahydrofuran; at -78℃; for 0.5h; | A solution of XXV-3 (2.9 g, 12.9 mmol) in THF (10 mL) was cooled to -78 C., DIBAl-H (24 mL, 24 mmol) was added and the resulting solution was stirred at -78 C. for 30 min., Then sat.NH4Cl was added to quench the reaction, extracted with EA, washed with brine, dried over Na2SO4 and concentrated, the residue was purified by flash chromatography (PE/EA=1/1) to give XXV-4 (1.5 g, yield: 51.7%) as a yellow solid. |
With diisobutylaluminium hydride; In tetrahydrofuran; chloroform; toluene; | Example 14c; step 5: A solution of 7-bromo-4H-chromen-4-one (26 g, 116 mmol) in dry THF (500 mL) under nitrogen for 1 hr, cooled to -80 C., and 173 mL of diisobutylaluminium hydride (2M in Toluene) was added over 30 minutes. The reaction was stirred at the same temperature for 30 min, quenched with a SiO2 (52 g)/water (52 mL) suspension, and allowed to warm to 0 C. The solution was filtered, the SiO2 washed with EtOAc, and the combined filtrate was concentrated to dryness. The residue was dissolved in CHCl3 (400 mL), washed with 1N NaOH (300 mL), dried over Na2SO4 and concentrated. Purification by chromatography on SiO2 (60-120 mesh) EtOAc/Pet ether (gradient elution 0-15%) afforded 7-bromochroman-4-one 18.1 g (69%) a pale yellow solid. LCMS 229.0 (M+2H); 1H NMR (DMSO-d6) 7.64-7.67 (d, 1H), 7.32 (s, 1H), 7.22-7.25(d, 1H), 4.53-4.57 (t, 2H), 2.76-2.80 (t, 2H). | |
With diisobutylaluminium hydride; In tetrahydrofuran; toluene; at -78℃; for 1.5h;Inert atmosphere; | To a solution of compound 1D (32.6 g, 145.5 mmol) in THF (600 mL) was added DIBAL (1 M in toluene, 437 mL, 437 mmol) dropwise under nitrogen at -78 for 30 minutes. The mixture was allowed to stir at -78 for 1 hour, then the reaction mixture was poured into 500 mL of 1 M aq. HCl, and extracted with ethyl acetate. The organic extract was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue obtained was purified using flash column chromatography on silica gel (petroleum ether: ethyl acetate 20: 1 to provide compound 1E as a solid. 1H-NMR (CDCl3, 400 MHz) : delta 7.72 (d, J 8.0 Hz, 1H) , 7.13-7.17 (m, 2H) , 4.52 (t, J 6.4 Hz, 1H) , 2.79 (d, J 6.4 Hz, 1H). |
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