Structure of 38427-94-0
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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. : | 38427-94-0 |
Formula : | C10H14N2O2 |
M.W : | 194.23 |
SMILES Code : | O=C(OC(C)(C)C)NC1=NC=CC=C1 |
MDL No. : | MFCD03411622 |
InChI Key : | ORUGTGTZBRUQIT-UHFFFAOYSA-N |
Pubchem ID : | 11206349 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H317 |
Precautionary Statements: | P280 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.4 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 54.48 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.22 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.0 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.12 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.74 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.36 |
Solubility | 0.853 mg/ml ; 0.00439 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.7 |
Solubility | 0.386 mg/ml ; 0.00199 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.98 |
Solubility | 0.204 mg/ml ; 0.00105 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 |
-6.06 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) |
2.23 |
* 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 |
---|---|---|
Under a nitrogen atmosphere, a solution of tert-butyl iV-(2-ρyridyl)carbamate (15.71 g, 80.9 mmol) and iV.ΛζN'.N'-tetramethylethylenediamine (TMEDA) (25.3 g, 218 mmol) in THF (400 mL) was cooled to -78 0C. M-Butyllithium (81 mL of a 2.5 M solution in hexanes) was added dropwise over a period of 20 minutes. The solution was stirred for ten minutes, and then the addition funnel was rinsed with additional THF (20 mL). The solution was warmed to -6 0C, stirred for two hours, and cooled again to -78 0C. Triisopropyl borate (57.7 g, 307 mmol) was added over a period often minutes. The resulting solution was warmed to 00C and then poured into saturated aqueous ammonium chloride (500 mL). A yellow solid formed and was stirred with diethyl ether (300 mL), isolated by filtration, washed with diethyl ether and water, and air-dried overnight to provide 2-ført-butoxycarbonylamino-3-pyridylboronic acid as a yellow solid. | ||
Manufacturing Example 1-7-22-N-butoxycarbonyl-3-pyridineboronic acid; A tetrahydrofuran solution (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylenediamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added dropwise over a period of 1 hour, which was stirred for 10 minutes. This mixture was warmed to a temperature between -10 C. and -6 C., which was stirred for 2 hours at that temperature. The solution was again cooled to -70 C., and triisobutyl borate (58 g) was added dropwise over a period of 1 hour. This mixture was warmed to 0 C., and then a saturated ammonium chloride aqueous solution was added thereto. Ether was added to the yellow solid thus produced, which was stirred, and the solid was then collected by filtration and washed with ether and water. This solid was dried under a reduced pressure, so as to obtain the title compound (14 g).1H-NMR spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-8.13 (2H, m). | ||
A solution of pyridin-2-yl-carbamic acid tert-butyl ester described in Preparation Example 4-1-1 (16 g) and N,N,N',N'-tetramethyl ethylenediamine (25 g) in tetrahydrofuran (400 mL) was cooled to -70 C., n-butyl lithium (78 mL, 2.64M heptane solution) was then added thereto dropwise over one hour, and stirred for 10 minutes. This mixture was heated to between -10 C. and -6 C., and stirred at this temperature for two hours. Again, this solution was cooled to 70 C., and triisobutyl borate (58 g) was added thereto dropwise over one hour. This mixture was heated to 0 C., then, a saturated aqueous ammonium chloride was added thereto. To the produced yellow solid was added ether, and stirred, and then, a solid was recovered by filtration and washed with ether and water. This solid was in vacuo to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Manufacturing Example 2-7-2 2-N-t-butoxycarbonyl-3-pyridineboronic acid; A solution of tetrahydrofuran (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 2-7-1 and N,N,N',N'-tetramethylethylene diamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64 M heptane solution) was added dropwise for 1 hour, and the mixture was stirred for 10 minutes. This mixture was then warmed to between -10 C. and -6 C., and stirred at that temperature for 2 hours. The solution was then cooled again to -70 C., and triisobutyl borate (58 g) was added dropwise for 1 hour. The mixture was warmed to 0 C., and saturated aqueous ammonium chloride solution was added thereto. To the resulting yellow solids was added ether and then stirred, and the solids were filtered out and washed with ether and water. The solids were dried under a reduced pressure to obtain the title compound (14 g).1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m). | ||
Manufacturing Example 1-7-2 2-tert-butoxycarbonylamino-3-pyridineboronic acid A solution of tetrahydrofuran (400 mL) of pyridin-2-yl-carbamic acid tert-butyl ester (16 g) described in Manufacturing Example 1-7-1 and N,N,N',N'-tetramethylethylene diamine (25 g) was cooled to -70 C., n-butyl lithium (78 mL, 2.64 M heptane solution) was added dropwise for 1 hour, and the mixture was stirred for 10 minutes. This mixture was then warmed to between -10 C. and -6 C., and stirred at that temperature for 2 hours. The solution was then cooled again to -70 C., and triisobutyl borate (58 g) was added dropwise for 1 hour. The mixture was warmed to 0 C., and saturated aqueous ammonium chloride solution was added thereto. To the resulting yellow solids was added ether and then stirred, and the solids were filtered and washed with ether and water. The solids were dried under a reduced pressure to obtain the title compound (14 g). 1H-NMR Spectrum (DMSO-d6) δ (ppm): 1.32-1.41 (9H, m), 6.80-6.84 (1H, m), 7.95-7.8.13 (2H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | To the reaction flask was added tert-butyl pyridin-2-ylcarbamate (0.7 g, 3.6 mmol), DMF (10 mL), and sodium hydride (0.32 g, 8 mmol, 60%).Stir at room temperature for 20 minutes, cool to 0 C in an ice bath.2-Chloro-5-chloromethylthiophene (0.6 g, 3.6 mmol) in DMF (5 mL) was slowly added dropwise.Stir at room temperature overnight.Ethyl acetate (100 ml) and water (50 ml) were added to the mixture. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated. Washing liquid: ethyl acetate: petroleum ether = 1:5), 1 g of butter was obtained, yield: 89%. |
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