Structure of 36052-24-1
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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. : | 36052-24-1 |
Formula : | C7H8N2O2 |
M.W : | 152.15 |
SMILES Code : | O=C(OC)C1=CN=C(N)C=C1 |
MDL No. : | MFCD00797844 |
InChI Key : | JACPDLJUQLKABC-UHFFFAOYSA-N |
Pubchem ID : | 737487 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 39.92 |
TPSA ? Topological Polar Surface Area: Calculated from |
65.21 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.44 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.68 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.46 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.15 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.84 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.11 |
Solubility | 1.17 mg/ml ; 0.0077 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.66 |
Solubility | 0.33 mg/ml ; 0.00217 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.73 |
Solubility | 2.87 mg/ml ; 0.0188 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 |
-6.04 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 |
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) |
1.54 |
* 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 |
---|---|---|
37% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 120 - 125℃; for 22h;Inert atmosphere; | a. Methyl 6-((3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinate (79). To a solution of 77 (1.1216 g, 3.99 mmol), 78(0.5910 g, 3.88 mmol), CsCO3 (3.1158 g, 9.58 mmol), rac-B1NAP (0.1856 g, 0.30 mmol) in toluene (4.5 mL) in a 100 mL round-bottomed flask was added Pd2(dba)3 (0.1755 g, 0.19 mmol). The solution was sparged with nitrogen for 5 mm., then a reflux condenser was fitted to the flask, the atmosphere was evacuated and back-filled with nitrogen (three times), and the reaction was heated to reflux with stirring in an oil bath (125-120 C) for 22h. After cooling the reaction to room temperature, excess cesium carbonate and other solid particulates were filtered and washed with ethyl acetate, and the organic filtrate was concentrated in vacuo to give a crude product that was purified by column chromatography (150 mE Si02, 6.5% ethyl acetate:hexanes to 10% ethyl acetate: hexanes) to give 79 (0.5072 g, 37%) as a crystalline solid, m.p. 169-175.8 C: ?H NMR (400 MHz, CDC13) 6 8.79 (dd, J= 2.4, 0.8, JH), 8.00 (dd, J= 8.8, 2.0, 1H), 7.25 (s, 1H), 7.18 (s, 1H), 7.05 (brs, 1H), 6.49 (dd,J 8.8, 0.8, 1H), 3.87 (s, 3H), 2.20 (s, 3H),1.68 (s, 4H), 1.29 (s, 6H), 1.25 (s, 6H); ?3C NMR (100.6 MHz, CDC13) 6 166.1, 160.0, 151.3, 143.8,143.0, 138.9, 134.1, 130.3, 129.1, 123.1, 116.1, 105.5, 51.7, 35.0, 34.9, 34.0, 33.9, 31.8, 31.8, 17.6; IR (neat) 2961, 1722, 1605, 1399, 1273 cm?; ES-MS (M+Na)+ calcd for C22H28N2O2Na 375.2048, found 375.2050. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
832 mg | With triethylsilane; trifluoroacetic acid; In acetonitrile; for 3h;Reflux; | In a round bottom flask, 6-amino-nicotinic acid methyl ester (90, 0.678 g, 4.46 mmol) was combined with <strong>[351410-62-3]5-fluoro-2-methoxy-pyridine-3-carbaldehyde</strong> (37, 0.532 g, 3.43 mmol), 10.6 mL of acetonitrile, trifluoroacetic acid (1.32 mL, 17.1 mmol) and triethylsilane (3.29 mL, 20.6 mol). The reaction was heated to reflux for 3 hours, then poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (91, 832 mg). MS (ESI) [M+H+]+=292.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In ethanol; at 70℃; | General procedure: Sodium carbonate (0.96 g, 9.06 mmol) was added after dissolving 6-aminonicotinate (1.5 g, 9.96 mmol) and G (2.2 g, 9.06 mmol) inethanol. The mixture was stirred at 70 C for 6 to 8 h. The solvent wasremoved under reduced pressure. The residue was added with waterand ethyl acetate to dissolve. The extracts were combined and washedby saturated brine. The organic phase was concentrated in vacuo afterdrying over anhydrous sodium sulfate and purified by column chromatographyto acquire expected compound H as a yellow solid. Yield1.13 g, 42.16%. 1H NMR (300 MHz, DMSO) δ 9.48 (s, 1H), 8.61 (s, 1H),8.33 (d, J = 9.6 Hz, 1H), 7.63 (s, 2H), 7.33 (t, J = 9.1 Hz, 1H), 7.24 -6.89 (m, 2H), 4.22 (q, J=7.5 Hz, 2H), 3.91 (s, 3H), 1.56 (t, J=7.4 Hz,3H). 13C NMR (75 MHz, DMSO-d6) δ 165.56, 156.44, 144.31, 132.01,129.58, 128.67, 124.23, 120.93, 116.26, 115.29, 114.45, 112.63,64.21, 52.73, 15.26. |
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