Structure of 479-27-6
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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. : | 479-27-6 |
Formula : | C10H10N2 |
M.W : | 158.20 |
SMILES Code : | NC1=C2C(N)=CC=CC2=CC=C1 |
MDL No. : | MFCD00004033 |
InChI Key : | YFOOEYJGMMJJLS-UHFFFAOYSA-N |
Pubchem ID : | 68067 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 0.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 52.76 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.04 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.16 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.78 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.02 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.53 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.56 |
Solubility | 0.437 mg/ml ; 0.00276 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.49 |
Solubility | 0.511 mg/ml ; 0.00323 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.34 |
Solubility | 0.072 mg/ml ; 0.000455 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 |
-6.0 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) |
1.0 |
* 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% | With copper(l) iodide; In 1,4-dioxane; at 150℃; for 1h;Microwave irradiation; | General procedure: A mixture of 1a (50 mg, 0.18 mmol), 1,8-diaminonaphthalene (2) (41.5 mg, 0.26 mmol), and CuI (3.3 mg, 0.018 mmol) in dioxane (1.0 mL) was stirred for 60 min at 150 C under microwave irradiation (300 W). The reaction mixture was concentrated under reduced pressure and purified by column chromatography over silica gel with hexane-EtOAc (15:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With zinc acetate hydrate; In methanol; at 20℃; for 16h;Inert atmosphere; | To a stirred solution of compound 39 (0.3 g, 1.82 mmol) inmethanol (5 mL) was added a solution of naphthalene-1,8-diamine (0.24 g, 1.52 mmol) in methanol(5 mL). Then Zn(OAc)2 (0.028 g, 0.128 mmol) was added and the mixture was stirred at roomtemperature for 16 h. The reaction mixture was filtered, the filter cake was washed with methanol,dried to get compound 40 (125 mg, 27percent), mp 92.3?94.8 °C. 1H-NMR (DMSO-d6) delta: 3.88 (s, 3H), 5.50(s, 1H), 6.54 (d, J = 7.6 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 7.08 (s, 2H), 7.16 (dd, J = 7.6 Hz, 8.0 Hz,2H), 7.67 (d, J = 8.0 Hz, 1H), 8.31 (dd, J = 2.0 Hz, 8.0 Hz, 1H), 9.08 (d, J = 2.0 Hz, 1H); MS (ESI):m/z calcd. for C18H16N3O2 [M+H]+ 306.1, found: 306.2. |
27.3% | With zinc acetate dehydrate; In methanol; at 20℃; | A mixture of 1,8-naphthalenediamine (0.24 g, 1.52 mmol)Was dissolved in methanol (5 mL)A solution of compound 26 (0.3 g, 1.82 mmol) in methanol was slowly added,After adding,Zinc acetate (0.028 g, 0.128 mmo 1) was added,Stirred at room temperature overnight,After completion of the reaction,Take the filter,washing,Drying and other measures to get the compound27 (150 mg,27.3percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | In methanol; for 6h;Reflux; | 1,8-diaminonaphthalene (3.0 g, 18.9 mmol,Tokyo Chemical Industry Co., Ltd.),9-Dulolidine carboxaldehyde (3.8 g, 31.6 mmol,Tokyo Chemical Industry Co., Ltd.) was dissolved in methanol (24 ml)And the mixture was stirred under heating reflux for 6 hours.After cooling to room temperature,The precipitate was collected by filtration,To give an intermediate product 1-d (5.7 g, yield 88.0%).Then,The resulting intermediate product 1-d (5.6 g, 16.4 mmol),Potassium carbonate (7.25 g, 52.4 mmol),A mixture of 1-iodobutane (10.56 g, 57.3 mmol) and N, N-dimethylformamide (56 ml) was placed in a 100 C. oil bath,And the mixture was heated and stirred for 6 hours.Water (56 ml) was added,Quench,The precipitate was collected by filtration,Purification by recrystallization,To obtain a compound (5.1 g, yield 68.5%) represented by the formula (6d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78.1% | With zinc acetate dehydrate; In methanol; at 20℃; for 15h; | A solution of <strong>[67808-64-4]methyl 5-formylthiophene-2-carboxylate</strong> 39 (645 mg, 3.79 mmol), 1,8-naphthalenediamine (500 mg,3.16 mmol), Zinc acetate dihydrate (58 mg,0.265 mmol) was dissolved in methanol (5 mL)The reaction was carried out at room temperature for 15 h,TLC test raw material reaction is completed.During the reaction, solid precipitates,The reaction solution was filtered,To give compound 40 (764.8 mg, 78.1percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In ethanol; for 5h;Reflux; | General procedure: In ethanolic solution,a mixture of 1,8-diaminonaphthalene 6 (0.40 g, 2.5 mmol)and ethyl aroyl pyrovate 10 (2.5mmol) was reuxed for 5 hrs. The reaction mixture was allowed to cool at room temperature,and then, the solid formed was collected by filltration,dried, and recrystallized from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.5% | In dimethyl sulfoxide; toluene; for 12h;Inert atmosphere; Molecular sieve; Dean-Stark; Reflux; | Under an argon atmosphere,(4-methyl-3-nitrophenyl) boronic acid (3.62 g, 20 mmol),1,8-diaminonaphthalene (4.8 g, 15 mmol)And 4mg molecular sieves 500mgIs dimethyl sulfoxide,Mixed solution of toluene55 mL (1:10 (v / v))Dissolved inRefluxed in the Dean-Stark apparatus for 12 hours.After confirming the completion of the reaction by thin-layer chromatography (also referred to as “TLC”),The reaction solution was cooled to around room temperature.Add 30 mL of water to the reaction solution,Extracted three times with 30 mL of ethyl acetate.The organic layer is dried over anhydrous magnesium sulfate (also called "MgSO4"),The solvent was distilled off.The residue was purified by silica gel column chromatography using n-hexane / ethyl acetate = 1/1 as an eluent to give compound (41).(5.55 g, 91.5% |