Structure of 161798-02-3
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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. : | 161798-02-3 |
Formula : | C14H12N2O3S |
M.W : | 288.32 |
SMILES Code : | O=C(C1=C(C)N=C(C2=CC=C(O)C(C#N)=C2)S1)OCC |
MDL No. : | MFCD15144699 |
InChI Key : | WTMZFYPEMMFHPR-UHFFFAOYSA-N |
Pubchem ID : | 135627703 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 11 |
Fraction Csp3 | 0.21 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 75.34 |
TPSA ? Topological Polar Surface Area: Calculated from |
111.45 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.64 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.48 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.87 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.96 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.9 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.77 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.96 |
Solubility | 0.0314 mg/ml ; 0.000109 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-5.5 |
Solubility | 0.000906 mg/ml ; 0.00000314 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.18 |
Solubility | 0.0188 mg/ml ; 0.0000653 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.59 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 |
0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.04 |
* 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 |
---|---|---|
99% | Example - 2: Preparation of Ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl thiozole - 5-carboxylateA mixture of 10. Og of Ethyl-2-(3-formyl-4-hydroxy phenyl)-4-methyl thiozole -5- carboxylate and 2.85 g of hydroxylamine hydrochloride were stirred for 30 minutes in 30 g of Dimethylformamide. To this reaction mixture 3.3 grams of acetyl chloride was added and stirred at 90°C for 2-3 hours. Reaction mass was cooled to room temperature and diluted with 100 ml of water and stir for 2 hours. The reaction mass was filtered and washed with purified water to give 10.0 g of Ethyl-2-(3-cyano-4-hydroxy phenyl)-4- methyl thiozole -5-carboxyltae (yield 99.0percent). | |
99.0% | Example-2 Preparation of Ethyl-2-(3-cyano-4-hydroxyphenyl)-4-methyl thiozole-5-carboxylate A mixture of 10.0 g of Ethyl-2-(3-formyl-4-hydroxy phenyl)-4-methyl thiozole-5-carboxylate and 2.85 g of hydroxylamine hydrochloride were stirred for 30 minutes in 30 g of Dimethylformamide. To this reaction mixture 3.3 grams of acetyl chloride was added and stirred at 90° C. for 2-3 hours. Reaction mass was cooled to room temperature and diluted with 100 ml of water and stir for 2 hours. The reaction mass was filtered and washed with purified water to give 10.0 g of Ethyl-2-(3-cyano-4-hydroxy phenyl)-4-methyl thiozole-5-carboxylate (yield 99.0percent). | |
97.6% | With formic acid; hydroxylamine hydrochloride; sodium acetate; at 100 - 105℃; for 10h; | In a 1 L four-necked flask, 60 g of a non-Bustam aldehyde substrate, 866.7 g of anhydrous formic acid, 17.3 g of hydroxylamine hydrochloride and24g anhydrous sodium acetate, stirring warming. The temperature of T = 100 ~ 105 , heat stirring 10h, the material vacuum distillation to no distillate to get the powdery solid compound . Weighing 86.8g, molar yield 97.6percent, purity (HPLC): 98.9percent, single impurity (HPLC): 0.22percent, total miscellaneous (HPLC): 1.1percent. |
85.9% | With formic acid; hydroxylamine hydrochloride; sodium formate; at 100℃; for 8h; | Example 3: Synthesis of ethyl-2-(3-cyano-4-hvdroxyphenvn-4-methyl-5-thiazole carboxylateHydroxylamine hydrochloride (35.82 g, 0.515 mol) and sodium formate (46.73 g, 0.687 mol) were added to a solution of ethyl-2-(3-formyl-4-hydroxyphenyl)-4-methyl-5- thiazole carboxylate (100 g, 0.343 mol) in formic acid (anhydrous, 300 mL) and the reaction mixture was heated to a temperature of about 100°C for about 8 hours. After completion of reaction, the reaction mixture was cooled to about 40°C and water was added to it. The reaction mixture was cooled to about 25°C and stirred for about 1 hour. The solid obtained was filtered, washed with water and dried. The solid was then dissolved in acetone at about 50°C and water was added slowly over a period of about 30 minutes. The mixture was cooled to about 25°C and again stirred for about 1 hour. The solid thus obtained was filtered, washed with acetone:water (1 :1) mixture and dried to obtain the title product. (Yield: 85 g, 85.9percent) |
42.6% | With ammonia; iodine; In tetrahydrofuran; water; at 25 - 30℃; | In a 50 mL round-bottomed flask charge under stirring 0.5g (1.72 mmol) of ethyl 2-(3-formyl-4- hydroxyphenyl)-4-methylthiazole-5-carboxylate in 8.6 mL THF, at 25-30 °C. Add 10.3 mL (544.94 mmol) 25percent aqueous ammonia, under stirring at 25-30 °C. Add 480 mg (1.89 mmol) iodine (I2) to the reaction mass, stir the reaction mixture at 25-30 °C for 15-30 min. Check the progress of the reaction by TLC (cyclohexane: ethyl acetate 1 :1). Starting material is consumed. Add 8.6 mL 5percent w/v aqueous thiosulfate and 40 mL ethyl acetate at the reaction mass, separate organic layer and extract aqueous layer twice with 40 mL ethyl acetate. Combine organic layers, dry over anhydrous sodium sulfate, filter off and concentrate to dryness. Purification of the residue with column chromatography (cyclohexane: ethyl acetate 3: 1) afforded 0.213 g of ethyl 2-(3-cyano-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (Formula Ilia). Yield : 42.6percent. |
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