Structure of 2437-17-4
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 2437-17-4 |
Formula : | C11H8O3 |
M.W : | 188.18 |
SMILES Code : | OC2=CC=C1C(=CC=CC1=C2)C(=O)O |
MDL No. : | MFCD00209983 |
InChI Key : | JCJUKCIXTRWAQY-UHFFFAOYSA-N |
Pubchem ID : | 5463800 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 52.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
57.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.21 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.02 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.84 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.2 |
Solubility | 0.12 mg/ml ; 0.000638 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.6 |
Solubility | 0.047 mg/ml ; 0.00025 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.87 |
Solubility | 0.252 mg/ml ; 0.00134 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) |
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 |
-5.5 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 |
0.56 |
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) |
1.0 |
* 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 |
---|---|---|
19.7 g | With aluminum (III) chloride; In N,N-dimethyl-formamide; at 135℃; for 6h; | In a 250ml four-necked bottle, add 20g of furoic acid, 23.2g of anisole, 100ml chlorobenzene, stirred and mixed; oil bath heated to internal temperature 35 ~ 40 C, slowly added 55.9g anhydrous aluminum trichloride; after the completion of the feed, stirring at 75-80 C for about 24 hours; cooling, concentrated distillation under reduced pressure Chlorobenzene After the distillation was completed, the temperature was lowered to room temperature, 60 ml of N,N-dimethylformamide was added to the reaction flask, and the mixture was stirred and mixed. At room temperature, 32.1 g of anhydrous aluminum trichloride was slowly and separately added; after the completion of the feeding, the oil bath was heated to The internal temperature is 135 C, and the reaction is kept for 6 hours; The water is cooled to room temperature; the reaction solution is slowly added to dilute hydrochloric acid solution for hydrolysis; extracted with ethyl acetate several times, and the ethyl acetate extract is combined, washed with water, and Ph is weakly acidic; The organic layer was concentrated under reduced pressure to recover ethyl acetate; The residue is decolorized and recrystallized with dilute alcohol water. Yielding 19.7 g of 6-hydroxy-1-naphthoic acid as a gray to pale yellow powder. Yield: 58.7%, melting point: 205.5 to 208.6 C, purity: 98.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In dimethyl sulfoxide; at 120℃; for 5h; | Example 43; Preparation OF 6- (7-METHOXY-QUINOLIN-4-YLOXY)-NAPHTHALENE-1-CARBOXYLIC acid methylamide; A. Preparation of Intermediate 43a:; 6-(7-Methoxy-quinolin-4-yloxy)-naphthalene-1- carboxylic acid A mixture of <strong>[68500-37-8]4-chloro-7-methoxy-quinoline</strong> (preparation described below) (200mg, 1. 036mmol), 6-hydroxy-1-naphthoic acid (200 mg, 1.062 MMOL), and Cs2CO3 (658 mg, 2.01 MMOL) IN 2 mL of DMSO was heated at 120°C in a seal tube for 5 hours, and cooled to room temperature. EtOAc and water were added. The aqueous layer was acidified with 1 N HCI until a precipitate was formed. The solid was filtered and washed with water, and dried in vacuum oven at 60°C overnight. The title compound (210 mg) was obtained as a brown solid NMR (300 MHz, DMSO-d6) 8 9.03 (d, 1H, J = 9.23 HZ), 8.64 (d, 1H, J = 5.08 Hz), 8.24 (d, 1H, J = 9.05 Hz), 8.17 (d, 2H, J= 7.73Hz), 7.91 (s, 1H), 7.72-7. 57 (m, 2H), 7.45 (d, 1H, J= 1.69 Hz), 7.36-7. 30 (m, 1H), 6.61 (d, 1H, J= 5.09 Hz), 3.95 (s, 3H). LCMS (ESI+) [M+H] /z CALC D 346, found 346 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With caesium carbonate; In dimethyl sulfoxide; at 20 - 140℃; for 3h; | Example 1 Preparation of 6-(6,7-dimethoxyquinazolin-4-yloxy)-1-naphthoic acid 6-Hydroxy-1-naphthoic acid (1.43 g, 7.6 mmol) and 38 ml of DMSO were stirred at room temperature while cesium carbonate (7.5 g, 22.9 mmol) and 4-chloro-6,7-dimethoxy-quinazoline (2.05 g, 9.14 mmol) were added. The mixture was heated at 140 C. for 3 hours. The mixture was cooled to room temperature and diluted with 40 mL of H2O. The mixture was neutralized with 2 N HCl to 6.5. The deposited solids were collected by vacuum filtration, washed with H2O, dried under vacuum and recrystallized from methanol to give the title compound (1.68 g, 59% yield) as a brown solid. LC-MS (m/z) 377 (M+1). |
59% | Example 1 Preparation of 6-(6,7-dimethoxyquinazolin-4-yloxy)-1-naphthoic acid 6-Hydroxy-1-naphthoic acid (1.43 g, 7.6 mmol) was dissolved in 38 ml of DMSO, then cesium carbonate (7.5 g, 22.9 mmol) and 4-chloro-6,7-dimethoxy-quinazoline (2.05 g, 9.14 mmol) were added. The mixture was heated at 140 C for 3 hours. When the reaction was finished the mixture was cooled to room temperature and diluted with 40 mL of H2O. The mixture was neutralized with 2 N HCl to pH=6.5. The deposited solids were filtered, washed with H2O, dried and recrystallized from methanol to give the title compound (1.68 g, 59% yield) as a brown solid. LC-MS (m/z) 377 (M+1). |