Structure of 1300750-50-8
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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. : | 1300750-50-8 |
Formula : | C6H6BF2NO3 |
M.W : | 188.92 |
SMILES Code : | FC(F)OC1=NC=CC=C1B(O)O |
MDL No. : | MFCD18261901 |
InChI Key : | YTNMJXVIJXDALS-UHFFFAOYSA-N |
Pubchem ID : | 71302322 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 40.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.58 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.01 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.2 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.84 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.73 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.79 |
Solubility | 3.06 mg/ml ; 0.0162 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.91 |
Solubility | 2.31 mg/ml ; 0.0122 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.26 |
Solubility | 10.3 mg/ml ; 0.0543 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 |
No |
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 |
-6.74 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) |
2.32 |
* 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 |
---|---|---|
With palladium diacetate; In water; at 200.0℃; for 0.08333330000000001h;Microwave irradiation; | General procedure: Palladium acetate (56 mg, 0.25 mmol) was added to a mixture of 5-fluoro-2-methoxyphenylboronic acid (850 mg, 5.0 mmol) and (R)-1-(4-bromophenyl)ethylamine (500 mg, 2.5 mmol) in water (20 ml). This mixture was heated for 5 min at 200 C in a Smithcreator microwave oven and then diluted with methanol (200 ml). The mixture was purified on a SCX column (20 g)using 2 M ammonia in methanol to elute the intermediate amine. Evaporation of solvents under reduced pressure gave (R)-1-(50-fluoro-2'-methoxybiphenyl-4-yl)-ethylamine as a gum (580 mg, 2.37 mmol, 96.6%).Triethylamine (41.1 ll, 0.295 mmol) and 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonyl chloride (24.5 mg, 0.0984 mmol) were added to a solution of (R)-1-(5'-fluoro-2'-methoxy-biphenyl-4-yl)-ethylamine (20 mg,0.082 mmol) in dichloromethane (1 ml) and the resulting solution shaken at room temperature overnight. Purification by preparative LCMS and removal of solvent under reduced pressure gave 19 (8.5 mg, 40%): |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100.0℃; for 0.5h;Microwave irradiation; | To a solution of 5-chloro-1-isopropyl-3-methyl-N-((5-methyl-1,3,4-oxadiazol-2-yl)methyl)-1H-pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 muetaiotaomicronIota) and (2-ethoxypyridin-3-yl)boronic acid (21 mg, 0.13 mmol) in dioxane (2 ml_) and H20 (0.7 ml_) was added Cs2C03(57 mg, 175 muetaiotaomicronIota) and Pd(1 ,1 '-bis(diphenylphosphino)ferrocene)Cl2(10 mg, 14 muetaiotaomicronIota). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 ml_) was added and the mixture was extracted with ethyl acetate (30 ml_chi3). The combined organic layers were washed with brine (20 ml_), dried over Na2S04and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to 5-(2-ethoxy-3-pyridyl)-1-isopropyl-3-methyl-N-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). 1H NMR (chloroform-d, 400 MHz) delta 8.28-8.26 (m, 1 H), 8.19-8.18 (m, 1 H), 7.23 (s, 1 H), 7.05- 7.02 (m, 1 H), 5.27 (brs, 1 H), 4.96-4.90 (m, 1 H), 4.71 (d, J = 1 .2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1 .43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR= 2.08 minutes (Method B). | |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 100.0℃; for 0.55h;Inert atmosphere; Microwave irradiation; | General procedure: To a solution of 5-chloro-l-isopropyl-3-methyl-//-((5-methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/- pyrazolo[4,3-b]pyridin-7-amine (50 mg, 70 pmol) and (2-ethoxypyridin-3-yl)boronic acid (21 mg, 0.13 mmol) in dioxane (2 mL) and H2O (0.7 mL) was added CS2CO3 (57 mg, 175 pmol) and Pd(l,l'- bis(diphenylphosphino)ferrocene)Cl2 (10 mg, 14 pmol). The mixture was purged with nitrogen for 3 minutes then stirred at 100C for 30 minutes under microwave irradiation. Water (30 mL) was added and the mixture was extracted with ethyl acetate (30 mL c 3). The combined organic layers were washed with brine (20 mL), dried over Na2S04 and concentrated. The crude mixture was purified by preparative TLC with dichloromethane: methanol = 20:1 twice, and then the crude product was further purified by preparative HPLC to give 5-(2-ethoxypyridin-3-yl)-l-isopropyl-3-methyl-//-((5- methyl-l,3,4-oxadiazol-2-yl)methyl)-l/-/-pyrazolo[4,3-b]pyridin-7-amine (6.1 mg). XH NMR (chloroform-d, 400 MHz) d 8.28-8.26 (m, 1H), 8.19-8.18 (m, 1H), 7.23 (s, 1H), 7.05-7.02 (m, 1H), 5.27 (brs, 1H), 4.96-4.90 (m, 1H), 4.71 (d, J = 1.2 Hz, 2H), 4.53-4.48 (m, 2H), 2.65 (s, 3H), 2.57 (s, 3H), 1.66 (d, J = 6.4 Hz, 6H), 1.43 (t, J = 6.8 Hz, 3H). LC-MS (m/z) 408.2 (MH+); tR = 2.08 minutes (Method B). |
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