Structure of 205448-66-4
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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. : | 205448-66-4 |
Formula : | C12H10ClNO3 |
M.W : | 251.67 |
SMILES Code : | O=C(C1=C(OC)C=C2N=CC=C(Cl)C2=C1)OC |
MDL No. : | MFCD17016133 |
InChI Key : | DDDSGYZATMCUDW-UHFFFAOYSA-N |
Pubchem ID : | 22646520 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 64.52 |
TPSA ? Topological Polar Surface Area: Calculated from |
48.42 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.6 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.64 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.87 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.95 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.55 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.3 |
Solubility | 0.126 mg/ml ; 0.0005 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.31 |
Solubility | 0.124 mg/ml ; 0.000493 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.53 |
Solubility | 0.0075 mg/ml ; 0.0000298 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-5.96 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.76 |
* 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 |
---|---|---|
88.97% | With ammonium hydroxide; In methanol; at 25 - 30℃; | 55.0 g of methyl 4-chloro-7-methoxyquinoline-6-carboxylate, 330 mL of methanol and 660 mL of 25% aqueous ammonia solution were taken in a flask at 25-3OoC and stirred for 10-12 hours. 275 mL of demineralized water was added to the above reaction solution and filtered. The filtered mass was washed with 165 mL of 15% methanolic solution and dried at 50- S5oCunder reduced pressure to obtain the title compound.Yield: 88.97%; HPLC Purity: 99.4 1% |
85.17% | With ammonium hydroxide; at 60℃; for 4h; | 4.1) In a 500 mL three-necked flask in which ammonia (200 mL, 5.2 mol) is placed, the compound IV (10 g, 39.8 mmol) obtained in the step 3.3) is added to obtain a mixture H;4.2) The mixture H obtained in step 4.1) was placed at 60 C, after 4 h reaction, cooled to room temperature to obtain a mixture I;4.3) Adding dichloromethane to the mixture I and extracting three times to obtain a pale yellow compound V (yield 85.17%) |
80% | With ammonia; water; In methanol; at 40℃; | Methyl 4-chloro-7-methoxy-quinoline-6-carboxylate (120 mg) was dissolved in methanol (6 ml), 28% aqueous ammonia (6 ml) was added thereto, and the mixture was stirred at 40C overnight. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography with a methanol-chloroform system to give 4-chloro-7-methoxy-quinoline-6-carboxylic acid amide (91 mg, yield 80%). 4-Chloro-7-methoxy-quinoline-6-carboxylic acid amide (91 mg), 5,6-dimethyl-[2,2']bipyridinyl-3-ol (115 mg), and 4-dimethylaminopyridine (141 mg) were dissolved in dimethylsulfoxide (3 ml), cesium carbonate (375 mg) was added to the solution, and the mixture was stirred overnight at 130C. The mixture was cooled to room temperature, and water was added to the reaction mixture. The organic layer was extracted with chloroform, and the chloroform layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography with a methanol-chloroform system to give the title compound (33 mg, yield 22%). 1H-NMR (CDCl3, 400 MHz): delta 2.40 (s, 3H), 2.67 (s, 3H), 4.13 (s, 3H), 5.92 (m, 1H), 6.39 (d, J = 5.4 Hz, 1H), 7.08 (ddd, J = 1.2, 4.9, 7.6 Hz, 1H), 7.36 (s, 1H), 7.56 - 7.63 (m, 2H), 7.76 (m, 1H), 7.90 (m, 1H), 8.40 (m, 1H), 8.54 (d, J = 5.6 Hz, 1H), 9.27 (d, J = 1.0 Hz, 1H) Mass spectrometric value (ESI-MS, m/z): 423 (M+Na)+ |
141 g | With formamide; sodium t-butanolate; In N,N-dimethyl-formamide; at 0 - 10℃; for 5h; | Formamide (221.74 ml) was added to pre-cooled mixture of compound of formula-6a (200 g) and dimethylformamide (1400 ml) at 0-5C. Sodium tertiary butoxide (152.72 g) was added in lot-wise to the reaction mixture at 5-l0C and stirred the reaction mixture for 5 hours at same temperature. The reaction mixture was quenched with pre-cooled water at 5-l0C and neutralized the mixture with aqueous hydrochloride solution. Heated the mixture to 40-45C and stirred the mixture for 1 hours at same temperature. Filtered the solid and washed with water. The obtained compound was recrystallized from the mixture of water and dimethylformamide and dried to get pure title compound. Yield: 141 g, Purity by HPLC: 99.91%, M.P: l98C (Decomposition) |
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