Structure of 3-Amino-4-fluorophenol
CAS No.: 62257-16-3
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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. : | 62257-16-3 |
Formula : | C6H6FNO |
M.W : | 127.12 |
SMILES Code : | OC1=CC=C(F)C(N)=C1 |
MDL No. : | MFCD09033850 |
InChI Key : | VJCSFNNTQGRAKH-UHFFFAOYSA-N |
Pubchem ID : | 13519180 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 32.83 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.25 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.8 |
Solubility | 2.01 mg/ml ; 0.0158 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.64 |
Solubility | 2.89 mg/ml ; 0.0227 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.7 |
Solubility | 2.52 mg/ml ; 0.0199 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) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.31 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 |
1.0 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) |
1.06 |
* 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 |
---|---|---|
39% | With iron; ammonium chloride; In ethanol; water; at 80℃; for 4h; | 3-Amino-4-fluorophenol 4-Fluoro-3-nitrophenol (300 mg, 1.91 mmol) was initially charged in water (12.5 ml) and ethanol (12.5 ml). Ammonium chloride (552 mg, 10.31 mmol) and iron filings (640 mg, 11.46 mmol) were added and the mixture was stirred at 80° C. for 4 h. The reaction mixture was then cooled to RT and filtered through kieselguhr, and the filtrate was extracted with ethyl acetate. The organic phase was dried, filtered and concentrated. 126 mg (39percent of theory) of the title compound were obtained. LC/MS (Method 6, ESIpos): Rt=0.99 min, m/z=128 [M+H]+. |
2.18 g (100%) | With H2;palladium on charcoal; In ethyl acetate; | Example 24 Preparation of 3-amino-4-fluorophenol (24) A mixture of <strong>[2105-96-6]4-<strong>[2105-96-6]fluoro-3-nitrophenol</strong></strong> (2.70 g, 17.2 mmol) and palladium on charcoal (10percent, 0.31 g) in 60 mL ethyl acetate is hydrogenated under 50 psi of H2 using a Parr hydrogenation reactor. After shaking for 1 hour, the reaction mixture is filtered using a diatomaceous earth pad to remove catalyst. The filtrate is concentrated in vacuo, and the residue is sublimed to yield 2.18 g (100percent) of Compound 24 as a white solid. MP: 142-144° C. 1 H-NMR (d6 -DMSO) 8.82 (s, 1H); 6.70 (dd, 1H); 6.17 (dd, 1H); 5.85 (m, 1H); 4.92 (s, 2H). 19 F-NMR (d6 -DMSO) 142.78 (t, 13.0 Hz). Anal. calc. for C6 H6 FNO: C, 56.69; H, 4.76; N, 11.02. Found: C, 57.28; H, 4.86; N, 10.65. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
860 mg | With 2-Picolinic acid; potassium phosphate; copper(l) iodide; In dimethyl sulfoxide; at 90℃; for 17h; | To a solution of compound B1 (2.48 g, 8.66 mmol), compound B2 (1.00 g, 7.87 mmol), pyridine-2-carboxylic acid (194 mg, 1.57 mmol) and K3PO4 (3.34 g, 15.7 mmol) in DMSO (15 mL) was added Cul (150 mg, 0.787 mmol), the mixture was purged with N2 for three times and stirred at 90C for 17 hours to give a dark solution. LCMS showed the reaction was completed. TLC showed the reaction was completed. The reaction mixture was poured into water (100 mL), extracted with EtOAc (100 mL x 2), the combined extracts was washed with brine (30 mL x 2), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by Combi flash to give compound B3 (860 mg) as light yellow oil. |