Structure of 825-22-9
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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. : | 825-22-9 |
Formula : | C7H6FNO2 |
M.W : | 155.13 |
SMILES Code : | C1=CC=C(C(=C1C(O)=O)N)F |
MDL No. : | MFCD01569395 |
InChI Key : | KUHAYJJXXGBYBW-UHFFFAOYSA-N |
Pubchem ID : | 586408 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 37.76 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.32 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.14 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.42 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.53 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.32 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.92 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.03 |
Solubility | 1.43 mg/ml ; 0.00925 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.35 |
Solubility | 0.686 mg/ml ; 0.00442 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.68 |
Solubility | 3.27 mg/ml ; 0.0211 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 |
-6.24 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 |
0.56 |
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) |
1.05 |
* 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 |
---|---|---|
80% | With sulfuric acid; for 66h;Heating; | Intermediate 10. A solution of 2-amino-3-fluorobenzoic acid (559 mg, 3.62 mmol) and 1.7 mL of concentrated H2S04 in 11 mL of anhydrous methanol was heated for 66 hours. After cooling to room temperature, methanol was concentrated under reduced pressure. Residue was taken up in 30 mL of water and added to a separatory funnel. Solid sodium carbonate was added slowly until gas evolution ceased (pH 9-10). Aqueous layer was extracted with ethyl acetate (3x40 mL). The combined organic layers were washed with 100 mL sat. NaHC03(aq) and 100 mL of Brine, separated, dried (MgS04), filtered, and concentrated under reduced pressure. Column chromatography (5% Ethyl Acetate in Hexanes) yielded intermediate 10 (491 mg, 80%) as a white solid.1H-NMR (CDC13, 300 MHz): delta 7.66-7.63(m, 1H), 7.15-7.08 (m, 1H), 6.60-6.55 (m, 1H), 5.40 (br s, 2H), 3.89 (s, 3H),LCMS m/z [M+H]+ C8H8FN02 requires: 170.05. Found 170.10 |
80% | With sulfuric acid; for 66h;Heating; | Example 104 Preparation of Intermediate 106 [0808] [0809] A solution of 2-amino-3-fluorobenzoic acid (559 mg, 3.62 mmol) and 1.7 mL of concentrated H2SO4 in 11 mL of anhydrous methanol was heated for 66 hours. After cooling to room temperature, methanol was concentrated under reduced pressure. The residue was taken up in 30 mL of water and added to a separatory funnel. Solid sodium carbonate was added slowly until gas evolution ceased (pH 9-10). The aqueous layer was extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with 100 mL sat. NaHCO300 and 100 mL of brine, separated, dried (MgSO4), filtered, and concentrated under reduced pressure. Column chromatography (5% ethyl acetate in hexanes) yielded intermediate 106 (491 mg, 80%) as a white solid. [0810] 1H-NMR (CDCl3, 300 MHz): delta 7.66-7.63 (m, 1H), 7.15-7.08 (m, 1H), 6.60-6.55 (m, 1H), 5.40 (br s, 2H), 3.89 (s, 3H), [0811] LCMS m/z [M+H]+ C8H8FNO2 requires: 170.05. Found 170.10 |
With hydrogenchloride; for 2h;Heating / reflux; | 2-amino-3-fluoro benzoic acid was dissolved in HCl (3 M solution in MeOH). The reaction mixture was heated to reflux for 2 h. Then, solvent was evaporated and the residue was partitioned between DCM and sat. sol. NaHCO3. The aqueous phase was separated and extracted several times withn DCM. The combined organic layers were dried (Na2SO4) and solvent was evaporated under reduced pressure to afford the title compound as a yellow oil.1H NMR (300 MHz, CDCl3) delta: 7.72-7.58 (m, IH), 7.18-7.02 (m, IH), 6.65-6.48 (m, IH), 3.88 (s, 3H). MS (ES) C8H8FNO2 requires: 169, found: 170 (M+H)+. |
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