Structure of 2346-26-1
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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. : | 2346-26-1 |
Formula : | C3H3NO3 |
M.W : | 101.06 |
SMILES Code : | O=C(N1)OCC1=O |
MDL No. : | MFCD02691902 |
InChI Key : | COWNFYYYZFRNOY-UHFFFAOYSA-N |
Pubchem ID : | 97389 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 23.01 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.37 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.47 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.79 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.39 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.53 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.17 |
Solubility | 68.3 mg/ml ; 0.675 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.23 |
Solubility | 59.9 mg/ml ; 0.593 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.2 |
Solubility | 63.3 mg/ml ; 0.627 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 |
-7.25 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 |
2.0 |
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) |
1.54 |
* 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 |
---|---|---|
55% | With potassium tert-butylate; In methanol; at 75℃; for 18h;Inert atmosphere; | [00227] A solution of glycolamide (2.10 g, 28 mmol), diethylcarbonate (4.06 mL, 34.0 mmol), and KOtBu (3.14 g, 28 mmol) in MeOH (30 mL) was heated to 75C for 18 h under N2 gas. The mixture was cooled to rt and concentrated under reduced pressure. The residue was diluted in a mixture of brine (100 mL) and 1M HCl (100 mL), and the aq phase was extracted with EtOAc (3X50 mL). The combined organic phases were dried over MgS04, filtered, and concentrated under reduced pressure to provide oxazolidine-2,4-dione as a solid (1.56 g, 55%). 1H NMR (300 MHz, DMSO) delta 11.8 (s, 1H), 4.75 (s, 2H)._ |
With potassium tert-butylate; In methanol;Heating / reflux; | To a solution of glycolamide (14 g, 186 mmol) and diethyl carbonate (27.1 mL, 224 mmol) in methanol (200 mL) was added potassium t-butoxide (20.8 g, 186 mmol). The reaction mixture was refluxed overnight, then cooled to room temperature. The solvent was removed in vacuo. The residue was dissolved in brine, acidified with 2N HCl, then extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give 8.0 g of oxazolidinedione as a white solid. | |
With sodium methylate; In methanol; for 1.5h;Reflux; | Step A: Oxazolidine-2,4-dione; To a solution of NaOMe (1.05 mmoles) in MeOH (21 ml) there are added 2-hydroxyacetamide (1 mmole) and diethyl carbonate (1.15 mmoles), and the reaction mixture is then heated at reflux for 1.5 hours. The reaction mixture is evaporated to dryness and then taken up in water. The aqueous phase is extracted with diethyl ether. The aqueous phase is acidified (pH 2) and then evaporated to dryness. The residue is triturated in AcOEt and filtered. The product obtained is purified on silica gel (c-Hexane/AcOEt; 1/1) to yield the title product in the form of a white powder. |
With potassium tert-butylate; In methanol; for 20h;Reflux; | Step 1 Oxazolidine-2,4-dione 2-Hydroxyacetamide (2.0 g, 26.6 mmol) and potassium tert-butoxide (3.0 g, 26.6 mmol) were dissolved in dry methanol (50 mL), added with diethyl carbonate (3.8 g, 31.9 mmol) and stirred at reflux for 20 hours. The reaction solution was cooled, concentrated under reduced pressure, dissolved in water and acidified to pH=2 with 6M hydrochloric acid solution. The mixture was extracted with ethyl acetate (100 mL*3), and the organic layer was washed with saturated brine and water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to give oxazolidine-2,4-dione (1.2 g, crude product). 1H NMR (400 MHz, DMSO) 4.75 (s, 2H), 3.91 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine; In dichloromethane; | PREPARATION A 3-Triphenylmethyl-1,3-<strong>[2346-26-1]oxazolidine-2,4-dione</strong> To a solution of 1,3-<strong>[2346-26-1]oxazolidine-2,4-dione</strong> (60.7 g, 0.600 mol) and triethylamine (60.7 g, 0.600 mol) in methylene chloride (500 mL) was added triphenylmethyl chloride (167.3 g, 0.600 mol). After 30 minutes, the thick white solid was collected by vacuum filtration, washed with water (2 L) and dried in a vacuum desicator to give the title compound (201.4 g, 96%). A portion was recrystallized from chloroform to give white plates: mp 216-218 C. |
With triethylamine; In chloroform; ethyl acetate; | C. 3-Triphenylmethyl-<strong>[2346-26-1]2,4-oxazolidinedione</strong> To a solution of 600 mg of <strong>[2346-26-1]2,4-oxazolidinedione</strong> and 601 mg of triethylamine in 7.0 ml of chloroform was added 1.66 g of triphenyl chloromethane and the reaction mixture stirred at room temperature for 30 minutes. The resulting mixture was dissolved in 250 ml of ethyl acetate and washed with water (3*50 ml) and brine (2*20 ml) and dried over sodium sulfate. Removal of the solvent gave 1.8 g of the desired product. | |
With triethylamine; In chloroform; ethyl acetate; | C. 3-Triphenylmethyl-<strong>[2346-26-1]2,4-oxazolidinedione</strong> To a solution of 600 mg of <strong>[2346-26-1]2,4-oxazolidinedione</strong> and 601 mg of triethylamine in 7.0 ml of chloroform was added 1.66 g of triphenyl chloromethane and the reaction mixture stirred at room temperature for 30 minutes. The resulting mixture was dissolved in 250 ml of ethyl acetate and washed with water (3 x 50 ml) and brine (2 x 20 ml) and dried over sodium sulfate. Removal of the solvent gave 1.8 g of the desired product. |
With triethylamine; In dichloromethane; at 20℃; for 0.666667h; | To a solution of the above obtained oxazolidinedione (4.6 g, 45 mmol) in CH2Cl2 (50 mL) were added TrCl (12.6 g, 45 mmol) and Et3N (6.3 mL, 45 mmol). The reaction mixture was stirred at room temperature for 40 min, then partitioned between water and EtOAc. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo to give the N-trityl OZD product. |
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