Structure of 51135-70-7
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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. : | 51135-70-7 |
Formula : | C11H12N2O2 |
M.W : | 204.23 |
SMILES Code : | O=C(C1=C2C=C(C)C=CN2N=C1)OCC |
MDL No. : | MFCD06739193 |
InChI Key : | DQUKVLJJYYYMFC-UHFFFAOYSA-N |
Pubchem ID : | 19770961 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H320-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.27 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 56.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.59 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.82 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.57 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.39 |
Solubility | 0.829 mg/ml ; 0.00406 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.18 |
Solubility | 1.35 mg/ml ; 0.00662 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.96 |
Solubility | 0.224 mg/ml ; 0.0011 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 |
-6.37 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.89 |
* 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 |
---|---|---|
59.8% | Stage #1: With N-hydroxy-2,4-dinitrobenzenamine In acetonitrile at 20℃; for 12 h; Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 10 h; |
2,4-Dinitrophenylhydroxylamine (13.00 g, 65.3 mmol) was added to a 500 mL vial, dissolved in 200 mL of acetonitrile, and 4-methylpyridine (9.12 g, 97.9 mmol) was added at room temperature for 12 h at room temperature. The solution was spun dry, 200 mL of DMF and potassium carbonate (27.07 g, 195.9 mmol) were added, ethyl propiolate (9.60 g, 97.9 mmol) was added in one portion, and reacted at room temperature for 10 h. The reaction was completed by TLC, and 300 mL of water and EA, liquid separation, water layer was extracted with 300 mL of EA, and the organic phase was combined, washed with 300 mL of brine, dried over anhydrous sodium sulfate, filtered and evaporatedElution with PE/EA=20/1-10/1 gave 7.97 g of pale yellow solid, yield 59.8percent. |
53% | Stage #1: With mesitylenesulfonylhydroxylamine In dichloromethane at 0℃; for 2 h; Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18 h; |
General procedure: These were made using MSH or DNPH as detailed below, unless otherwise stated. A fresh solution of MSH23 in CH2Cl2 (1 equiv) was added to the substituted pyridine (1 equiv) in CH2Cl2 (10 mL) at 0 °C. After 2 h, the solvent was removed in vacuo. Alternatively, a solution of DNPH12 (1 equiv) and the substituted pyridine (1 equiv) in MeCN (40 mL) was heated at 40 °C for 18 h. The solvent was removed in vacuo. The method continues by taking the residue from either method in dry DMF (8 mL), and then ethyl propiolate (1 equiv) and K2CO3 (2 equiv) were added, and the suspension stirred at room temperature for 18 h. The reaction mixture was diluted with water and extracted twice with EtOAc. The combined organic phases were washed three times with water then with brine, dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with a hexanes: EtOAc gradient, unless otherwise stated) gave the pyrazolo[1,5-a]pyridine. |
53% | Stage #1: With mesitylenesulfonylhydroxylamine In dichloromethane at 0℃; for 2 h; Stage #2: With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18 h; |
Step 2.1 : A fresh solution of O-(mesitylsulfonyl)hydroxylamine in CH2CI2 (6.0 ml_, 0.44 mol L"1, 2.6 mmol) [T. Eichenberger et al., HeIv. Chim. Acta 1986, 69(6), 1521] was added to 4-methylpyridine (1: X = Me) (248 mg, 2.66 mmol) in CH2CI2 (10 mL) at 0 0C. After 2 h, the solvent was removed in vacuo. The residue was taken up in dry DMF (8 mL), then ethyl propiolate (0.25 mL, 2.5 mmol) and K2CO3 (450 mg, 3.26 mmol) were added, and the suspension stirred at room temperature for 18 h. The reaction mixture was diluted with water and extracted twice with EtOAc. The combined organic phases were washed three times with water then with brine, dried (Na2SO4) and the solvent removed in vacuo. Chromatography (eluting with hexanes: EtOAc 97:3 to 95:5 to 9:1) gave ethyl 5-methyl- pyrazolo[1 ,5-a]pyridine-3-carboxyIate (4: X = Me) as a pale brown solid (175 mg, 53percent). 1H NMR δ (400 MHz, CDCI3) 8.39 (d, J 7.1 Hz, 1 H)1 8.34 (s, 1H), 7.93 (s, 1H), 6.76 (dd, J 7.1 , 1.9 Hz, 1 H), 4.38 (q, J 7.1 Hz, 2H), 2.47 (s, 3H), 1.41 (t, J 7.1 Hz, 3H). LCMS (APCI+) 205 (MH+, 100percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In N,N-dimethyl-formamide at 100℃; for 2 h; | A solution of ethyl 5-bromopyrazolo[1,5-ajpyridine-3-carboxylate (1.0 g, 3.73 mmol),methylboronic acid (448 mg, 7.46 mmol), Pd(dppf)C12 (545 mg, 0.746 mmol) and C52CO3(2.42 g, 7.46 mmol) was dissolved in DMF (5.0 mL), then the mixture was stirred at 100 °Cfor two hours. It was concentrated, and purified by silica gel chromatography with PE:EA=5: 1to obtain the desired compound as an orange solid (589 mg, 77percent). ESI MS m/z = 204.5[M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.73 g | Stage #1: With perchloric acid In tetrahydrofuran at 0℃; for 1.5 h; Stage #2: at 0 - 35℃; Stage #3: With potassium carbonate In N,N-dimethyl-formamide at 10 - 35℃; |
To a solution of ethyl N-(mesitylsulfonyl)oxyacetoimidate (14.7 g) in THF (15 mL) was added 60percent perchloric acid (11.2 mL) at 0°, the mixture was stirred for 90 min, and to the reaction mixture was added ice water. The insoluble substance was collected by filtration, washed with water, and dried under stream. The residue was added to a solution of 4-methylpyridine (4.18 mL) in THF (80 mL) at 0° C., and the mixture was stirred overnight at room temperature. The solvent was evaporated under reduced pressure, DMF (80 mL), ethyl propionate (5.21 mL) and potassium carbonate (11.9 g) were added thereto, and the mixture was stirred overnight at room temperature. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with 1N hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.73 g). 1H NMR (300 MHz, CDCl3) δ 1.41 (3H, t, J=7.2 Hz), 2.47 (3H, s), 4.38 (2H, q, J=6.9 Hz), 6.77 (1H, dd, J=7.0, 1.7 Hz), 7.93 (1H, s), 8.34 (1H, s), 8.39 (1H, d, J=7.2 Hz). |
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