Structure of 113512-57-5
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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. : | 113512-57-5 |
Formula : | C6H3F2NO3 |
M.W : | 175.09 |
SMILES Code : | OC1=CC([N+]([O-])=O)=C(F)C=C1F |
MDL No. : | MFCD08443942 |
InChI Key : | SMRYCTJAGPDVEH-UHFFFAOYSA-N |
Pubchem ID : | 10921024 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H315-H317-H318-H410 |
Precautionary Statements: | P261-P264-P270-P272-P273-P280-P301+P312+P330-P302+P352-P305+P351+P338+P310-P333+P313-P391-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 37.2 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.03 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.42 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.24 |
Solubility | 1.01 mg/ml ; 0.00579 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.6 |
Solubility | 0.441 mg/ml ; 0.00252 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.76 |
Solubility | 3.05 mg/ml ; 0.0174 mol/l |
Class? Solubility class: Log S scale |
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) |
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 |
-6.23 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 |
1.0 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.93 |
* 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 |
---|---|---|
96% | carbon palladium; In nitrogen; ethyl acetate; | (3) 24.9 g (142 mmol) of the above 2,4-difluoro-5-nitrophenol was dissolved in 150 mL of ethyl acetate, 5.0 g of 10% palladium/carbon was added and the mixture was stirred at 50 to 60 C for 27 hours under a stream of hydrogen. The gaseous phase in the reaction vessel was substituted with nitrogen, the reaction solution was filtered by suction and the solvent was distilled off under reduced pressure. The residue was triturated with n-hexane to give 19.8 g of 5-amino-2,4-difluorophenol (yield: 96%). NMR (90MHz, CDCl3) delta (ppm) 4.75 (brs, 2H), 6.37 (t, 1H, J=9.1Hz), 6.87 (t, 1H, J=11.1Hz), 9.21 (s, 1H) MS (M/Z) 145 (M+) Molecular formula C6H5F2NO=145 |
96% | With hydrogen;palladium dihydroxide; In ethyl acetate; for 6h; | To a suspension of 2,4-difluoro-5-nitrophenol (1.01 g, 5.77 mmol) in EtOAc was added palladium hydroxide (0.08 g, 0.57 mmol) and the resulting slurry was stirred under a hydrogen atmosphere for 6 h. The mixture was filtered through a Celite pad, washing with EtOAc (2*10 mL) and the filtrate was concentrated to afford 5-amino-2,4-difluorophenol (0.8 g, 96% yield) as a solid. 1H NMR (400 MHz, DMSO-d6) delta 9.28 (s, 1H), 6.91 (t, J=7.2 Hz, 1H), 6.35 (t, J=8.8 Hz, 1H), 4.84 (brs, 2H); MS (ESI) m/z: 146.0 (M+H+). |
96% | With hydrogen; palladium(II) hydroxide; In ethyl acetate; for 6h; | To a suspension of 2,4-difluoro-5-nitrophenol (1.01 g, 5.77 mmol) in EtOAc was added palladium hydroxide (0.08 g, 0.57 mmol) and the resulting slurry was stirred under a hydrogen atmosphere for 6h. The mixture was filtered through a Celite pad, washing with EtOAc (2x10 mL) and the filtrate was concentrated to afford 5-amino-2,4- difluorophenol (0.8 g, 96% yield) as a solid. FontWeight="Bold" FontSize="10" H NMR (400 MHz, DMSO-i/6) delta 9.28 (s, 1H), 6.91 (t, J = 7.2 Hz, 1H), 6.35 (t, J = 8.8 Hz, 1H), 4.84 (brs, 2H); MS (ESI) m/z: 146.0 (M+H+). |
94.6% | With palladium 10% on activated carbon; hydrogen; In ethyl acetate; at 20℃; for 16h; | To a stirred solution of 2,4- difluoro-5-nitrophenol (1, 25 g, 0.143 mol) in EtOAc (200 mL), 10% Pd/C (4.55 g, 0.043 mol) was added. The reaction mixture was stirred at RT under H2 for 16 h. After the reaction completion (TLC), the reaction mixture was filtered by using celite bed, washed with EtOAc (1000 mL) and concentrated under reduced pressure to afford 5-amino-2,4- difluorophenol (2) as off brown solid (20.10 g, 94.6%); LCMS (ESI positive ion) m/z: calculated: 145.03; observed: 146.2 (M+l). |
palladium on activated carbon; In nitrogen; ethyl acetate; | 2,4-Difluoro-5-nitrophenol (24.9 g, 142 mmol) obtained above was dissolved in ethyl acetate (150 mL) and 10% palladium on activated carbon (5.0 g) was added to the mixture. The reaction mixture was stirred under hydrogen stream at 50 to 60 C for 27 hours. After the atmosphere in reactor was replaced with nitrogen, the reaction mixture was filtrated with suction. The solvent in filtrate was distilled off under reduced pressure, the residue was triturated with hexane to give 5-amino-2,4-difluorophenol (19.8 g, yield: 96%). 1H NMR (90 MHz, CDCl3) delta (ppm) 4.75 (brs, 2H), 6.37 (t, J = 9.1 Hz, 1H), 6.87 (t, J = 11.1 Hz, 1H), 9.21 (s, 1H) EI-MS (m/e) 145 M+molecular formula C6H5F2NO = 145 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iron(III) chloride; In water; | EXAMPLE A10: 2,4-difluoro-5-nitrophenol 50 g of (2,4-difluoro-5-nitro)-phenyl trifluorochloro-ethyl ether and 25 ml of tetramethylene sulphone are initially introduced, and 50 ml of concentrated sulphuric acid and 0.5 g of iron(III) chloride are added. The mixture is then heated at 100 C. for 3 hours, and cooled, and 100 g of ice are added in order to subsequently reflux for a further 2 hours. After 250 ml of water had been stirred in, the product was extracted repeatedly with toluene, and the toluene phase was dried and distilled. 24 g of 2,4-difluoro-5-nitrophenol are obtained. Boiling point: 160-2 C./24 mbar, m.p. 117-19 C. |