Structure of 504413-35-8
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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. : | 504413-35-8 |
Formula : | C9H5BrF3N3O |
M.W : | 308.06 |
SMILES Code : | O=C(NC1=CN2C=C(Br)C=CC2=N1)C(F)(F)F |
MDL No. : | MFCD11976190 |
InChI Key : | BUYPVRDWQVLXDL-UHFFFAOYSA-N |
Pubchem ID : | 12065953 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 57.4 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.08 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.67 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.78 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.34 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.88 |
Solubility | 0.0402 mg/ml ; 0.000131 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.72 |
Solubility | 0.0585 mg/ml ; 0.00019 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.81 |
Solubility | 0.0477 mg/ml ; 0.000155 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) |
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 |
-5.99 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.15 |
* 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 |
---|---|---|
77% | With water; lithium hydroxide In tetrahydrofuran at 20℃; for 24 h; | Intermediate 6: 6-bromoimidazo[1 ,2-a]pyridin-2 -amine A solution of Λ/-(6-bromoimidazo[1 ,2-a]pyridin-2-yl)-2,2,2-trifluoroacetamide (5.5 g, 18.2 mmol) and lithium hydroxide (1.2 g, 27.3 mmol) in THF/Water (5OmL, 7:3) was stirred at room temperature for 24h. THF was then removed under reduced pressure and the aqueous layer was extracted with DCM. Combined organic layers were then washed with brine, dried over sodium sulphate and concentrated under reduced pressure to give the titled compound as a pale brown solid (2.9 g, 77percent). HPLC (X-Terra), Rt: 3.07 min (purity: 97.0percent). LC/MS (Atlantis), M+(ESI): 214.1.1H-NMR (DMSO-d6, 400 MHz) δ 8.58-8.59 (1 H, s), 7.11-7.13 (1 H, d), 7.05-7.07 (1 H, d), 6.98 (1 H1 S), 5.19 (2H, s). |
42% | With methanol; water; potassium carbonate In tetrahydrofuran at 60℃; for 16 h; | Step 4. 6-bromoimidazo[1,2-a]pyridin-2-amine To a 250 mL round-bottomed flask was added N-(6-bromoH-imidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoroacetamide (3.50 g, 11 mmol), THF (15 mL), methanol (15 mL), water (15 mL) and potassium carbonate (16 g, 114 mmol). The mixture was stirred at 60° C. for 16 h. After cooling to rt, the mixture was poured into water (100 mL) and extracted with CH2Cl2 (4*75 mL). The combined extracts were washed with brine, dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (0.5 to 5.0percent MeOH/CH2Cl2) afforded the title compound (1.01 g, 42percent). MS (ESI, positive ion) m/z: 212 (M(79Br)+1). |
8.3 g | With sodium hydroxide In ethanol at 80℃; | A mixture of A81-3 (15 g, crude, 46 mmol) in 1 N NaOH/EtOH (50 mL/40 mL) was stirred at 80°C overnight. After cooled to r.t., the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over Na2S04 and the solvent was removed by vacuum. The residue was recrystallized in petroleum ether to give a brown solid (8.3 g, 85percent). H NMR (400 MHz, DMSO-d<5) δ 8.60 (s, 1H), 7.32 -7.05 (m, 2H), 7.00 (s, 1H), 5.22 (s, 2H). |
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