Structure of 499-51-4
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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. : | 499-51-4 |
Formula : | C7H5NO5 |
M.W : | 183.12 |
SMILES Code : | OC(=O)C1=CC(O)=CC(=N1)C(O)=O |
MDL No. : | MFCD00066478 |
Boiling Point : | No data available |
InChI Key : | XTLJJHGQACAZMS-UHFFFAOYSA-N |
Pubchem ID : | 8743 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 40.18 |
TPSA ? Topological Polar Surface Area: Calculated from |
107.72 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
-0.25 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.18 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-2.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.32 |
Solubility | 8.69 mg/ml ; 0.0475 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.04 |
Solubility | 1.66 mg/ml ; 0.00909 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.2 |
Solubility | 116.0 mg/ml ; 0.634 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 |
No |
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 |
-7.26 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) |
1.72 |
* 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 |
---|---|---|
85% | With thionyl chloride; at 0 - 20℃;Inert atmosphere; Reflux; | Compound 4 was synthesized as described previously [19]. First, 12.6 mL (173 mmol) thionyl chloride was added to 50 mL of anhydrous ethanol in a round-bottom flask under argon flow cooled in an ice bath. Then, 5.03 g (27 mmol) chelidamic acid was added in small portions, and the mixture was stirred for 5 min at 0 C. The mixture was stirred for 20 h at room temperature, followed by 2 h at reflux. The solvent was removed under reduced pressure. The flask with the crude product was placed in an ice bath, and 50 mL water was added. The mixture was neutralized with 5 mL of 10% aqueous Na2CO3 and 5 mL of 50% aqueous ethanol. The precipitate was filtered and dried under reduced pressure. The product was obtained as a white solid (5.49 g (85%)). 1H NMR (400 MHz, ACN-d3) delta 7.65 (s, 2H), 4.39 (q, J = 7.1 Hz, 4H), 1.37 (t, J = 7.1 Hz, 6H). |
83.92% | With thionyl chloride; at 90℃; for 3h; | To a solution of 4-hydroxypyridine-2,6-dicarboxylic acid (183 g, 1.0 mol) in EtOH (1500ml) was added thionyl chloride (200 ml, 2.0 mol) at room temperature and the mixture washeated at 90?C for 3 h. The mixture was cooled to room temperature, concentrated to dryness. The crude was added water 1 L and stirred at room temperature and neutralized with sodium carbonate, after filtered and washed with water (200 ml*3) to give white solid (201g, yield:83.92%). ?HNMR(CD3OD-d4) oe 7.45 (s, 1 H), 4.40 (dd, 4 H, J=7.2 Hz), 1.40 (t, 3H, J=6.8Hz). |
70% | With sulfuric acid; at 100℃; for 4h; | The reaction was performed under air. Chelidamic acid (2 g, 9.9 mmol) was dissolved in a mixture of ethanol (75 mL) and concentrated sulfuric acid (95-97%, 1.3 mL). It was refluxed at 100 C (bath temperature) for 4 h (not more). Ethanol was rotor-evaporated. The residue was neutralized with NaHCO3 and extracted with CH2Cl2. The organic layer was washed with water and rotor-evaporated to give oil. The oil was dried under vacuum. Ether (3-5 mL) and, then, heptane (20 mL) were added to it. Brief sonication of this mixture gave a suspension of white solid product. It was filtered and washed with ice-cold heptane (10 mL). Ether induces rapid crystallization of the product, which facilitates the work-up. The product was checked by TLC and 1H NMR. If necessary, it was re-crystallized again from ether/heptane to remove the 4-ethoxy substituted by-product. White solid: 1.647 g (6.9 mmol, 70%; C11H13NO5; MW 239.22). |
63% | With sulfuric acid; In water; for 16h;Reflux; | The compound 37 was prepared according to the procedure described in the article Chemistry-A European Journal 2008, 14, 1726. The chelidamic acid monohydrate 5 (3 g, 15 mmol) was heated at reflux in EtOH (60 ml) in the presence of 97% sulfuric acid (0.6 ml) for 16 h. The solvent was evaporated under reduced pressure, the white residue remaining was neutralized with a saturated aqueous solution of sodium bicarbonate and extracted with DCM. The organic phase was dried with magnesium sulfate, evaporated to dryness and the diester 37 was obtained in the form of a white solid (2.27 g, 63%). Rf=0.10 (silica, CH2Cl2/MeOH 99/1); 1H NMR (CDCl3, 300 MHz) delta 7.31 (s, 2H), 4.46 (q, J=7.1 Hz, 4H), 1.42 (t, J=7.1 Hz, 6H); 13C NMR (DMSO-d6, 62.5 MHz) delta 166.0, 164.3, 149.9, 115.2, 61.4, 14.1. |
56% | With thionyl chloride; at 0℃;Heating / reflux; | Example 35; 411 412 413Part A To chelidamic acid monohydrate 403 (12.89 g, 64.1 mmol) in ethanol (100 ml) in an ice bath was added thionyl chloride (5 ml_) slowly. The ice bath was removed and the reaction mixture was heated to reflux overnight. The ethanol was removed in vacuo and the residue was dissolved in ethyl acetate (50 ml_). The mixture was washed with saturated sodium bicarbonate until the aqueous layer was no longer acidic. The organic layer was washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated to afford a tacky white solid (11.64 g). Recrystallization of the white solid (9.25 g) from ethyl acetate/hexane/DCM afforded a crystalline white solid (7.44 g, 56%) 1H NMR (300 MHz, CDCI3) delta 7.31 (bs, 2H), 4.43 (q, 4H, J = 7.1 Hz), 1.40 (t, 6H, J = 7.1 Hz). |
With toluene-4-sulfonic acid;Industry scale; Reflux; | Reference Example 2-1; 4-hydroxypyridin-2.6-dicarboxylic acid diethyl esterIn ethanol (60.0 L) was dissolved 4-hydroxypyridin-2,6-carboxylic acid hydrate (3.00 kg). To the solution was added p-toluenesulfonic acid monohydrate (514 g), and the mixture was heated to reflux overnight. The reaction solution was concentrated under reduced pressure, a saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was washed with a saturated saline solution and dried over anhydrous sodium sulfate. Insoluble matters were filtered out, and the filtrate was concentrated under reduced pressure to give the title compound (3.48 kg) as a yellow oil. mass :240(M+ 1)+ . | |
With toluene-4-sulfonic acid; In water;Reflux; | Reference Example 2-1 4-hydroxy-2,6-pyridinedicarboxylic acid diethyl ester In ethanol (60.0 L) was dissolved 4-hydroxy-2,6-pyridinecarboxylic acid hydrate (3.00 kg). To the solution was added p-toluenesulfonic acid monohydrate (514 g), and the mixture was heated to reflux overnight. The reaction solution was under reduced pressure, a saturated aqueous sodium hydrogencarbonate solution was added to the residue, and the mixture was extracted with chloroform. The organic layer was washed with a saturated saline solution and dried over anhydrous sodium sulfate. Insoluble matters were filtered out, and the filtrate was under reduced pressure to give the title compound (3.48 kg) as a yellow oil. mass: 240 (M+1)+. |
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