Structure of 23432-43-1
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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. : | 23432-43-1 |
Formula : | C9H6ClNO |
M.W : | 179.60 |
SMILES Code : | OC1=CC=NC2=CC=C(Cl)C=C12 |
MDL No. : | MFCD00024011 |
InChI Key : | XXGUQCVVGPZTPF-UHFFFAOYSA-N |
Pubchem ID : | 220929 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
33.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.63 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.59 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.76 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.6 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.96 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.33 |
Solubility | 0.835 mg/ml ; 0.00465 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.5 |
Solubility | 5.65 mg/ml ; 0.0315 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.74 |
Solubility | 0.0327 mg/ml ; 0.000182 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 |
-6.54 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) |
1.24 |
* 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% | Add 6-chloro-4-oxo-2,3-dihydroquinoline (0.01 mol) to a 25 ml reaction flask, add 15 ml of acetonitrile, acetic acid (0.01 mol), stir for 20 minutes, and slowly add hydrogen peroxide (0.03). Mol), the reaction was stirred at 65 C, the progress of the reaction was monitored by TLC, and the reaction was stopped after 7 hours. After the reaction liquid is cooled to room temperature, it is poured into 50 ml of water, stirred and filtered to obtain a crude product of 5-dichloro-4-hydroxyquinoline, which is separated by silica gel column chromatography (column chromatography silica gel 100-200 mesh, eluent) Petroleum ether: ethyl acetate = 1:4), and the eluent was concentrated to give the product. The yield was 88%, and the purity was 96%; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In diphenylether; at 220℃; for 0.666667h; | General procedure: A solution of compound 2 in phenoxybenzene was prepared. The mixture was stirred for 40 min at 220 C. The mixture was cooled to room temperature and hexane was added. The solids were collected by filtration and washed with hexane to provide the target compound. The compound was used without further purification. 4-hydroxyquinoline-6-carbonitrile (3a) 3a was prepared by the methods described above from 5-(((4-R-phenyl)amino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (2), where R is carbonitrile, to prepare a white solid (yield 65%). ESI-MS m/z: 171 ([M+H]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | In diphenylether; at 240℃; for 0.5h;Heating / reflux; | A mixture of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid, 21.62 g, 0.15 mol) and trimethyl orthoformate (150 mL) was heated to a gentle reflux under nitrogen for 1 hour. The resulting red solution was cooled (80 C.) and 4-chloroaniline (19.14 g, 0.15 mol) was added portionwise resulting in the formation of a yellow solid. The reaction mixture was heated to reflux, stirred vigorously for an additional hour, and then cooled to 25 C. (see Ryan et al. (2006) Org. Lett. 8:2779-2782; Madrid et al. (2005) Bioorg. Med. Chem. Lett. 15:1015-1018). The resulting solid was filtered and washed with cold acetone to afford the ene-amine compound (29.58 g, 70%, mp. 214-214.5 C. (dec.)) as yellow solid which was characterized by 1H NMR. To a solution diphenyl ether (20 mL) at 240 C. was added the ene-amine compound (5 g, 17.75 mmol) in small portions resulting in vigorous gas evolution and the reaction was bought to reflux for 30 minutes under nitrogen. The reaction mixture was allowed to cool to 80 C. and the precipitate was isolated by filtration and washing with acetone and hexane until the filtrate was colorless. The brown solid was purified by digestion with ether followed by distillation under reduced pressure to give 6-chloroquinolin-4-ol as light-yellow solid in 55% yield (1.7533 g, m.p. 281-282.5 C. (see Riegel et al., (1946) J. Am. Chem. Soc. 68:1264-1266, m.p. 274-275 C.). 1H NMR (400 MHz, CDCl3): 6.07 (1H, d, J=7.4 Hz), 7.59 (1H, d, J=8.8 Hz), 7.68 (1H, dd, J=8.8, 2.5 Hz), 7.95 (1H, d, J=7.4 Hz), 8.01 (1H, d, J=2.4 Hz), 11.92 (1H, bs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(b) 6-Chloro-4-hydroxyquinoline From 6-chloro-4-hydroxyquinoline-3-carboxylic acid ethyl ester, reacted in a manner similar to that described in Example 12, there was obtained the above-named compound of mp 265-268 after recrystallization from ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With formaldehyd; In sodium hydroxide; | (a) <strong>[23432-43-1]6-Chloro-4-hydroxyquinoline</strong> was reacted with formaldehyde in aqueous sodium hydroxide at 55 for 24 hours to give the novel compound 6-chloro-4-hydroxy-3-hydroxymethylquinoline, m.p. >300. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a suspension solution of <strong>[23432-43-1]6-chloroquinolin-4-ol</strong> (2.16 g, 12 mmol), triphenylphosphine (3.78 g, 14.4 mmol, 1.2 eq.), and 3-bromo-1-propanol (1.30 ml, 14.4 mmol, 1.2 eq.) in dry tetrahydrofuran (40 mL) was added diethyl azodicarboxylate (2.51 g, 14.4 mmol, 1.2 eq.) at 25 C. over 20 minutes under nitrogen and the reaction mixture was left stirring for an additional hour. Hydrobromic acid (1.36 mL, 12 mmol, 48% aqueous solution, 1.0 eq.) was added resulting in white solid as the corresponding hydrobromide salt. The white salt was filtered and digested with three times of diethyl ether. The white salt was neutralized by aqueous potassium carbonate solution and followed by extraction with dichloromethane. Upon evaporation of the dichloromethane layers gave the crude product which was subjected to purify by column chromatography (silica gel, 2% methanol in CH2Cl2 as eluent) to provide the bromo compound as white solid (2.52 g, 70%, m.p. 102-103.5 C. (dec.)). 1H NMR (500 MHz, CDCl3): 2.50 (2H, m), 3.70 (2H, t, J=6.3 Hz), 4.36 (2H, t, J=5.8 Hz), 6.79 (1H, d, J=5.3 Hz), 7.64 (1H, dd, J=9.0, 2.4 Hz), 7.99 (1H, d, J=9.0 Hz), 8.14 (1H, d, J=2.4 Hz), 8.75 (1H, d, J=5.2 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium t-butanolate; In N,N-dimethyl-formamide; at 20℃; for 1.5h;Inert atmosphere; Irradiation; | General procedure: To a screw-capped test tube equipped with a magnetic stir bar was added 1a (0.2 mmol, 1.0 eq.) and t-BuONa (38.4 mg, 0.4 mmol, 2.0 equiv.). Then, air was withdrawn and backfilled with N2 (three times). Perfluorobutyl iodide 2a (103.8 mg, 0.3 mmol, 1.5 equiv.) and DMF (2.0 mL) was added by syringe. Thereafter, the test tube was stirred under green LED (15 W) irradiation at room temperature. After 90 min, the resulting mixture was diluted with HCl (1 mol/L) and extracted with EtOAc (10 mL×3). The organic layer was washed with brine and dried over MgSO4, concentrated in vacuo and purified by column chromatography (1:1 hexane/EtOAc) to afford the desired product 3a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With diphenyl phosphoryl azide; 1,8-diazabicyclo[5.4.0]undec-7-ene; In toluene; for 1h;Reflux; | General procedure: DBU (31 mul, 0.21 mmol) and DPPA (47 mul, 0.22 mmol) were added to the phenol solution (0.20 mmol) in toluene (1.0 mL). After stirring for 0.25-16 h at rt or reflux, the mixture was diluted with AcOEt (30 mL). Next, the mixture was washed with saturated aqueous NaHCO3 (25 mL) and brine (25 mL) before being dried over Na2SO4. Concentration of the solvent in vacuo, followed by purification of the residue on a silica gel column (AcOEt:n-hexane 1:1-1:20), gave the desired aryl azide. |