Structure of 16066-84-5
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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. : | 16066-84-5 |
Formula : | C6H13NO2 |
M.W : | 131.17 |
SMILES Code : | O=C(OC(C)(C)C)NC |
MDL No. : | MFCD08899404 |
InChI Key : | JHLVEBNWCCKSGY-UHFFFAOYSA-N |
Pubchem ID : | 527635 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H312-H315-H319-H332-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501 |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.83 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 35.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.06 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.93 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.14 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.08 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.0 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.04 |
Solubility | 11.9 mg/ml ; 0.091 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.32 |
Solubility | 6.26 mg/ml ; 0.0477 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.18 |
Solubility | 8.63 mg/ml ; 0.0658 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 |
-6.44 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) |
1.53 |
* 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 |
---|---|---|
74% | With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In 1,4-dioxane; at 100℃; for 13.5h; | Compound a70 (1.0g, 4.15mmol) was dissolved in dioxane (16 mL), tert-butyl methyl carbamate (653mg, 4.98mmol), 2- dicyclohexylphosphino-2 ', 4', 6'-triisopropyl biphenyl (297mg, 0.622mmol), potassium phosphate (2.20g, 10.73mmol)And tris (dibenzylideneacetone) palladium(190mg, 0.207mmol) was added, and the mixture was stirred for 5 hours at 100°C .Tertiary butyl methyl carbamate (218mg, 1.66mmol),2-dicyclohexyl phosphino-2 ', 4', 6'-triisopropyl biphenyl(99mg, 0.207mmol),Potassium phosphate (0.73g, 3.57mmol)And tris (dibenzylideneacetone) palladium (0)(63.3mg, 0.069mmol) was added and stirred for 3 hours and a half.Tertiary butyl methyl carbamate (435mg, 3.32mmol),2-dicyclohexyl phosphino-2 ', 4', 6'-triisopropyl-biphenyl (99 mg, 0.207 mmol) and tris (dibenzylideneacetone) palladium (0) (63.3 mg, 0.069 mmol) was added to 5 hours It was semi-stirring.Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography - (hexanes-ethyl acetate) to give compound a71 (0.75 g, 74percent yield). |
74% | With potassium phosphate; XPhos; In 1,4-dioxane; at 100℃; for 13.5h; | Step 1 Preparation of Compound c71 (0551) Compound c70 (1.0g, 4.15mmol) was dissolved in dioxane (16mL), and tertiary butyl methyl carbamate (653mg, 4.98mmol), 2- dicyclohexylphosphino-2 ', 4' , 6'-triisopropyl-biphenyl (297mg, 0.622mmol), potassium phosphate (2.20g, 10.73mmol) and tris (dibenzylideneacetone) palladium (190mg, 0.207mmol) were added to the mixture at 100 °C for 5 hours. Tertiary butyl methyl carbamate (218mg, 1.66mmol), 2-dicyclohexylphosphino-2 ', 4', 6'-triisopropyl biphenyl (99mg, 0.207mmol), potassium phosphate (0.73g, 3.57mmol) and tris (dibenzylideneacetone) palladium (0) (63.3mg, 0.069mmol) were added to the mixture and the mixture was stirred for 3 hours. Tertiary butyl methyl carbamate (435mg, 3.32mmol), 2- dicyclohexylphosphino-2 ', 4', 6'-triisopropyl biphenyl (99mg, 0.207mmol) and tris (dibenzylideneacetone) palladium (0) (63.3mg, 0.069mmol) was then added to the mixture and the mixture was stirred for 5.5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give compound c71 (0.75g, 74percent yield). [M + H] = 244.95, Method Condition 3: retention time 2.08 min |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 100 - 105℃; for 12h;Inert atmosphere; | 24 g (120 mmol) of <strong>[1206972-45-3]2-chloro-5-(trifluoromethoxy)pyridine</strong>, 19.1 g (150 mmol) of tert-butyl N-methylcarbamate and 17.5 g (180 mmol) of sodium tert-butoxide were dissolved in 400 ml of toluene, 2.8 g (3 mmol) of tris(dibenzylideneacetone)dipalladium(0) and 1.73 g (3 mmol) of Xantphos were added under argon, and the mixture was stirred at 100-105 C. for 12 h. Subsequently, the mixture was filtered through Celite and the solvent was distilled off under reduced pressure. |
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