Structure of 77837-09-3
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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. : | 77837-09-3 |
Formula : | C13H11NO3 |
M.W : | 229.23 |
SMILES Code : | O=C(C(C=C1)=CN(C2=CC=CC=C2)C1=O)OC |
MDL No. : | MFCD07369505 |
InChI Key : | RJBSPLUQQNNULO-UHFFFAOYSA-N |
Pubchem ID : | 11989075 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.08 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 63.32 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.52 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.03 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.92 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.54 |
Solubility | 0.656 mg/ml ; 0.00286 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.14 |
Solubility | 1.65 mg/ml ; 0.0072 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.71 |
Solubility | 0.0449 mg/ml ; 0.000196 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 |
-6.62 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) |
2.04 |
* 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 |
---|---|---|
79% | 6-Oxo-1-phenyl-1,6-dihydropyridine-3-carboxylic acid: Lithium hydroxide monohydrate (0.366 g, 8.73 mmol) was added to a mixture of methyl-6-oxo-1-phenyl-1,6-dihydropyridine-3-carboxylate (1.0 g, 4.37 mmol), tetrahydrofuran (9 mL) and water (6 mL) at 0° C. The mixture was stirred for 1 hour, diluted with water and washed with ethyl acetate. The pH of the aqueous layer was adjusted to 2 using 2 N hydrochloric acid and the precipitate was filtered to give the title compound as a brown solid (0.740 g, 79percent). m.p. 256-263° C.; 1H NMR (400 MHz, DMSO-d6) delta 6.53 (d, J=9.4 Hz, 1H), 7.40-7.49 (m, 5H), 7.87 (dd, J=2.5, 9.8 Hz, 1H), 8.23 (d, J=2.5 Hz, 1H); IR (KBr) nu 3446, 1708, 1645, 1577, 1263, 1228 cm-1; MS 214 (M-1). | |
79% | Step 3; 6-Oxo-l -phenyl- 1 ,6-dihydropyridine-3-carboxylic acid:; Lithium hydroxide monohydrate (0.366 g, 8.73 mmol) was added to a mixture of methyl-6-oxo-l -phenyl- 1,6- dihydropyridine-3-carboxylate (1.0 g, 4.37 mmol), tetrahydrofuran (9 mL) and water (6 mL) at 0 °C. The mixture was stirred for 1 hour, diluted with water and washed with ethyl acetate. The pH of the aqueous layer was adjusted to 2 using 2 N hydrochloric acid and the precipitate was filtered to give the title compound as a brown solid (0.740 g, 79percent). m.p. 256-263 °C; *H NMR (400 MHz, DMSO-d6) delta 6.53 (d, / = 9.4 Hz, 1H), 7.40-7.49 (m, 5H), 7.87 (dd, / = 2.5, 9.8 Hz , 1H), 8.23 (d, / = 2.5 Hz, 1H); IR (KBr) upsilon 3446, 1708, 1645, 1577, 1263, 1228 cm"1; MS 214 (M - 1). | |
67% | With water; lithium hydroxide; In methanol; at 50℃; for 5h; | General procedure: Example 1-3 Synthesis of 6-oxo-1-phenyl-1,6-dihydro-3-pyridinecarboxylic acid [0042] After 750 mg (3.27 mmol) of methyl 6-oxo-1-phenyl-1,6-dihydro-3-pyridinecarboxylate was dissolved in 9 mL of methanol and 3 mL of water, 235 mg (9.81 mmol) of lithium hydroxide was added to the solution. Afterward, the resulting reaction solution was stirred at about 50° C. for about 5 hours. After termination of the reaction was determined by liquid chromatography, the solvent was removed in vacuo, followed by addition of aqueous HCl to titrate a pH of the reaction product to pH 2. After filtration of the resulting solid compound (Actual yield: 470 mg, Percent yield: 67percent), the resulting compound was used without purification. [0043] 1H-NMR (DMSO-d6,200 MHz) delta8.18 (s, 1H), 7.88 (d, 1H), 7.49 (m, 5H), 6.54 (d, 2H) |
A round-bottom flask was charged with methyl 6-oxo-l -phenyl- l ,6-dihydropyridine-3- carboxylate 12a (2.26 g, 9.87 mmol), THF (58.5 mL) and MeOH (14.6 mL). The resulting slurry was cooled to 0 C. A solution of LIOH (700 mg, 29.2 mmol) in water (29.2 niL) was added dropwise via cannula. After stirring for 5 minutes the ice bath was removed. The mixture was stirred at rt for 45 minutes and then at 35 C for 30 minutes. After cooling to rt, the mixture was acidified to pH 1 with 1 N HCl and extracted with EtOAc (3 times). The combined organic layers were washed with brine, dried (Na?SO4), filtered, and concentrated in vacuo to afford 1.95 g of a brown solid which was used without further purification,[128] A round-bottom flask was charged with 1.30 g of the brown solid, THF (35.8 niL) and MeOD (8.94 ml). A solution of NaOD (99,5 atom percent D, 1.86 ml, 40 wt. percent in D2O) was added. After stirring at rt for 1.5 h, the mixture was cooled to 0 C. acidified to pH 1 with DCl (35 wt. percent in D2O), and extracted with EtOAc (3times). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo to afford 1.31 g (100 percent) of the title compound 22 as a brown solid. 1H NMR (DMSOd6): delta 8.22 (d, J= 2.4, 1H), 7.91 (dd, J- 2.7, 9.1, 1H), 7.62-7,48 (m, 5H), 6.58 (d. ,/ = 9.44, 1H). MS (M+H): 216.1. | ||
With water; lithium hydroxide; In methanol; at 50℃; for 5h; | After 750 mg (3.27 mmol) of methyl 6-oxo-1-phenyl-1,6-dihydro-3-pyridinecarboxylate was dissolved in 9 mL of methanol and 3 mL of water, 235 mg (9.81 mmol) of lithium hydroxide was added to the solution. Afterward, the resulting reaction solution was stirred at about 50°C for about 5 hours. After termination of the reaction was determined by liquid chromatography, the solvent was removed in vacuo, followed by addition of aqueous HCl to titrate a pH of the reaction product to pH 2. After filtration of the resulting solid compound (Actual yield: 470 mg, Percent yield: 67 percent), the resulting compound was used without purification.[60] 1H-NMR(DMSO-d6,200MHz)delta8.18(s,1H),7.88(d,1H),7.49(m,5H),6.54(d,2H) |
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