Structure of 383134-85-8
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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. : | 383134-85-8 |
Formula : | C9H9FO3 |
M.W : | 184.16 |
SMILES Code : | O=C(O)CC1=CC(F)=CC=C1OC |
MDL No. : | MFCD00671771 |
Boiling Point : | No data available |
InChI Key : | WGZCWKASVDIAOH-UHFFFAOYSA-N |
Pubchem ID : | 302684 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.67 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.46 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.88 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.98 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.76 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.05 |
Solubility | 1.66 mg/ml ; 0.00901 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 1.67 mg/ml ; 0.00905 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.58 |
Solubility | 0.481 mg/ml ; 0.00261 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 |
-6.39 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 |
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) |
1.71 |
* 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 |
---|---|---|
91% | Example 65 2-(5-fluoro-2-methoxyphenyl)-N-(5-(4-fluorophenyl)-11-methyl-1-oxo-2,4,5,11-tetrahydro-1H-2,5,11-triazadibenzo[cd,h]azulen-8-yl)acetamide [0760] A stock solution of Example 23e and N,N-diisopropylethylamine (0.09 M and 0.25 M in N,N-dimethylacetamide, respectively, 450 muL, 0.2 mmol Example 23e and 0.6 mmol N,N-diisopropylethylamine), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.14 M in N,N-dimethylacetamide, 450 muL, 0.3 mmol), and <strong>[383134-85-8]2-(5-fluoro-2-methoxyphenyl)acetic acid</strong> (0.40 M in N,N-dimethylacetamide, 125 muL, 0.24 mmol) were aspirated from their respective source vials, mixed through a perfluoroalkoxy mixing tube (0.2 mm inner diameter), and loaded into an injection loop. The reaction segment was injected into the flow reactor (Hastelloy coil, 0.75 mm inner diameter, 1.8 mL internal volume) set at 100 C., and passed through the reactor at 180 muL min-1 (10 minute residence time). Upon exiting the reactor, the reaction mixture was loaded directly into an injection loop and purified using reverse phase HPLC(C8, acetonitrile/water (0.1% TFA), 5-100%) to give 0.0243 g (91%) of the title compound as the TFA salt. 1H NMR (400 MHz, DMSO-d6/D2O) delta 10.28 (s, 1H), 8.12 (d, J=2.44 Hz, 1H), 7.65 (s, 1H), 7.42 (dd, J=8.54, 2.44 Hz, 1H), 7.20 (d, J=8.54 Hz, 1H), 7.11 (m, 2H), 7.04 (s, 1H), 7.01 (m, 1H), 6.83 (m, 2H), 6.48 (m, 2H), 5.02 (d, J=15.56 Hz, 1H), 4.18 (d, J=15.87 Hz, 1H), 4.04 (s, 3H), 3.79 (s, 3H), 3.70 (s, 2H). MS (APCI+) m/z 527.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of 2-(5-chloro-2-methoxy-phenyl)acetic acid (2.26 g, 11.27 mmol) in thionylchloride (8.13 mL, 92.21 mmol) was heated at 70 00 for 30 minutes. After cooling to roomtemperature, excess thionyl chloride was removed in vacuo, azeotroping with toluene. The resulting residue was dissolved in DCM (5 mL) and added to a solution of 4-amino-N-tert- butyl-pyridine-2-carboxamide (step 1) (2.0 g, 10.25 mmol) and DIPEA (2.15 mL, 12.29 mmol) in DCM (25 mL). The mixture stirred at room temperature for 1 hour and then dilutedwith water (50 mL) and extracted with DCM. The combined organic extracts were washed with brine (50 mL), dried over Na2504 and concentrated in vacuo. The crude residue was purified by chromatography on silica eluting with 0-50% EtOAc in heptane to afford the titled compound as a pale orange powder.1H NMR (500 MHz, Chloroform-d) O 8.39 (d, J = 5.6 Hz, 1H), 8.20 (dd, J = 5.6, 2.2 Hz, 1H), 8.10 (brs, 1H), 7.98 (brs, 1H), 7.56 (d, J = 2.1 Hz, 1H), 7.29-7.26 (m, 2H), 6.89 (d,J = 9.5 Hz, 1H), 3.94 (5, 3H), 3.70 (5, 2H), 1.47 (5, 9H).LC-MS (Method E): Rt 1.21 mins; MS m/z 376.1/ 378.1 = [M+H]+ (92% 215nm) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In 1,4-dioxane; ethyl acetate; at 20℃; for 2h; | A mixture of ethyl 3-aminobenzoate (300 mg, 1.82 mmol) and 2-(5-fluoro-2-methoxy- phenyl)acetic acid (334 mg, 1.82 mmol) in 1,4-dioxane (5 mL) was treated with 50% T3P solution in EtOAc (2.31 mL, 1.82 mmol) and TEA (634 muL, 3.63 mmol). After stirring at room temperature for 2 hours, the mixture was partitioned between water (20 mL) and EtOAc (20 mL). The organic layer was separated, dried over Na2SO4 and concentrated in vacuo. Purification of the crude residue by chromatography on silica eluting with EtOAc in heptane afforded the titled compound as a white solid.1H NMR (500 MHz, DMSO-d6) delta 10.31 (s, 1H), 8.26 (t, J = 1.8 Hz, 1H), 7.86- 7.82 (m, 1H , 7.63 dt, J = 7.79, 1.2 Hz, 1H , 7.45 t, J = 7.9 Hz, 1H), 7.11 (dd, J = 9.2, 3.1 Hz, 1H),Hz, 1H), 4.31 (q, J = 7.1 Hz, 2H), 3.75 [M+H]+ (100% 215nm) |
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