Structure of 15463-09-9
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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. : | 15463-09-9 |
Formula : | C10H9NO |
M.W : | 159.19 |
SMILES Code : | OC1=CC=C2C(C)=CC=NC2=C1 |
MDL No. : | MFCD06245596 |
InChI Key : | GXFFWHIKMRPHIV-UHFFFAOYSA-N |
Pubchem ID : | 135491854 |
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 | 0.1 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.73 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.65 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.49 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.44 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.02 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.86 |
Solubility | 0.219 mg/ml ; 0.00138 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.58 |
Solubility | 0.417 mg/ml ; 0.00262 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.5 |
Solubility | 0.0503 mg/ml ; 0.000316 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 |
-5.67 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) |
1.09 |
* 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 |
---|---|---|
With sodium hydroxide; potassium carbonate; In N,N-dimethyl-formamide; at 100.0℃; for 5.0h; | Example 4 A mixture of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (225mg, 0.67mmol), (prepared as described for the starting material in Example 1), potassium carbonate (106mg, 0.77mmol) and <strong>[15463-09-9]7-hydroxy-4-methylquinoline</strong> (122mg, 0.77mmol), (Chem. Berich. 1967, 100, 2077), in DMF (7.5ml) was stirred at 100C for 5 hours then allowed to cool to ambient temperature. The reaction mixture was treated with 1M aqueous sodium hydroxide solution (40ml) and stirred at ambient temperature for a few minutes. The crude solid was collected by filtration washing with water. The resultant solid was dissolved in dichloromethane (2ml) and was filtered through phase separating paper. The filtrate was evaporated under vacuum to give a solid residue which was triturated with ether, filtered and dried to give 6-methoxy-4-(4-methylquinolin-7-yloxy)-7-(3-morpholinopropoxy)quinazoline (175mg, 57%). 1H NMR Spectrum: (DMSOd6) 1.98(m, 2H); 2.39(m, 4H); 2.48(t, 2H); 2.71 (s, 3H); 3.59(m, 4H); 4.00(s, 3H); 4.26(t, 2H); 7.40(s, 1H); 7.41(m, 1H); 7.61(dd, 1H); 7.62(s, 1H); 7.90(d, 1H); 8.20(d, 1H); 8.52(s, 1H); 8.78(d, 1H) MS (ESI): 461 (MH)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 15 Using a procedure analogous to that described for Example 9, 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (0.13g, 0.4mmol), (prepared as described for the starting material in Example 9), was reacted with <strong>[15463-09-9]7-hydroxy-4-methylquinoline</strong> (80mg, 0.5mol), (Chem. Berich. 1967, 100, 2077), to give 6-methoxy-4-(4-methylquinolin-7-yloxy)-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (155mg, 87%). 1H NMR Spectrum: (DMSOd6) 1.7(br s, 4H); 2.05(m, 2H); 2.5(br s, 4H); 2.6(t, 2H); 2.75(s, 3H); 4.02(s, 3H); 4.3(t, 2H); 7.41(s, 1H); 7.45(d, 1H); 7.65(s, 1H); 7.65(d, 1H); 7.95(s, 1H); 8.25(d, 1H); 8.55(s, 1H); 8.8(d, 1H) MS (ESI): 445 [MH]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 13 Using a procedure analogous to that described for Example 10, 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (130mg, 0.4mmol), (prepared as described for the starting material in Example 10), was reacted with 4-methyl-7-hydroxyquinoline (80mg, 0.5mol), (Chem. Ber. 1967, 100, 2077), to give 6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)-4-(4-methylquinolin-7-yloxy)quinazoline (160mg, 90%). 1H NMR Spectrum: (DMSOd6) 1.3-1.5(m, 2H); 1.7-1.95(m, 3H); 1.9(t, 2H); 2.17(s, 3H); 2.74(s, 3H); 2.8(d, 2H); 4.07(s, 3H); 4.1(d, 2H); 7.4(m, 2H); 7.65(dd, 1H); 7.65(s, 1H); 7.9(s, 1H); 8.21(d, 1H); 8.54(s, 1H); 8.78(d, 1H) MS (ESI): 445 [MH]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 100.0℃; for 2.0h; | Example 155 A mixture of 4-chloro-6-methoxy-7-(3-(N -methyl-N -methylsulphonylamino)propoxy)quinazoline (150 mg, 0.42 mmol), (prepared as described for the starting material in Example 152), potassium carbonate (90 mg, 0.63 mmol) and <strong>[15463-09-9]7-hydroxy-4-methylquinoline</strong> (71 mg, 0.46 mmol), (Chem. Berich. 1967, 100, 2077), in DMF (5.0 ml) was stirred at 100 C for 2 hours and allowed to cool to ambient temperature. The DMF solvent was removed by evaporation and the residue was taken up in 2N aqueous sodium hydroxide solution. The precipitate was filtered off, dried, taken up in dichloromethane and then filtered through phase separating paper. The solution was then evaporated to dryness. The resulting solid was recrystallized from acetonitrile, filtered and washed with diethyl ether to give 6-methoxy-7-(3-(N -methyl-N -methylsulphonylamino)propoxy)-4-(4-methylquinolin-7-yloxy)quinazoline (84mg, 42%). 1H NMR Spectrum: (DMSOd6) 2.09 (m, 2H), 2.71 (s, 3H), 2.79 (s, 3H), 2.89 (s, 3H), 3.25 (t, 2H), 3.98 (s, 3H), 4.25 (t, 2H), 7.37 (s, 1H), 7.38 (d, 1H), 7.61 (dd, 1H), 7.63 (s, 1H), 7.89 (d, 1H), 8.20 (d, 1H), 8.54 (s, 1H) and 8.76 (d, 1H) MS (ESI): 483 (MH)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With di-tert-butyl-diazodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20.0℃; | To a solution of intermediate 24 (700 mg, theoretically 1 .94 mmol) and 4- mcthylquinolin-7-ol (370 mg, 2.32 mmol ) in THF (20 mL) were added triphenylphosine (624 mg, 2.71 mmol) and DBAD ( 71 1 mg. 2.71 mmol). The mixture was stirred overnight at room temperature and was then evaporated in vacuo. The crude was purified by preparative LC ( irregular SiOH, 15-40 mupiiota, 50 g, Merck, dry loading (Celite) mobile phase gradient: from Heptane 80%, EtOAc 18%, MeOH 2% to Heptane 10%, EtOAc 81%, MeOH 9%) to give intermediate 73 as an off-white foam (697 mg, 67% yield). |
A429970 [1807542-80-8]
7-Methoxy-4-methylquinoline hydrochloride
Similarity: 0.95