Structure of 912444-89-4
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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. : | 912444-89-4 |
Formula : | C14H23NO4 |
M.W : | 269.34 |
SMILES Code : | O=C(N1CCC(C(OCC)=O)=CCC1)OC(C)(C)C |
MDL No. : | MFCD11114566 |
InChI Key : | OQQBVXIIESRTAD-UHFFFAOYSA-N |
Pubchem ID : | 25194565 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.71 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 76.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.2 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.75 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.25 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.5 |
Solubility | 0.852 mg/ml ; 0.00316 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.01 |
Solubility | 0.265 mg/ml ; 0.000985 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.02 |
Solubility | 2.6 mg/ml ; 0.00964 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) |
Yes |
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 |
-6.38 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 |
1.0 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) |
3.34 |
* 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 |
---|---|---|
95% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene at 60℃; for 1 h; | EXAMPLE 42D; 1-tert-butyl 4-ethyl 2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate A solution of example 42C (0.77 g, 2.1 mmol) in 30 mL of benzene was treated with DBU (0.9 ml ) at 60° C. for 1 hour. After cooling, the reaction mixture was concentrated and the residue was purified by flash column chromatography (30percent EtOAc in hexane) to give the title product (540 mg, 95percent yield). MS (DCI/NH3) m/z 270 (M+H)+. |
3.31 g | With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 60℃; | A solution of 1-(tert-butyl) 4-ethyl 5-((methylsulfonyl)oxy)azepane-1,4-dicarboxylate (5.0 g, 13.7 mmol)and DBU (10 mL) in toluene (50 mL) was heated to 60° C.and stirred overnight. Upon completion of the reaction, thereaction mixture was quenched with water (70 mL) andextracted with EtOAc (100 mLx3). The combined organicphase was dried over Na2S04 and concentrated underreduced pressure. The residue was purified by silica-gelcolunm chromatography to afford 3.31 g of 1-(tert-butyl)4-ethyl 2,3,6,7 -tetrahydro-1H-azepine-1 ,4-dicarboxylate asa yellow oil. LC-MS (ESI+ ): m/z 292 [M+Nat. |
56.8 g | With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran | To a solution of 1-tert-butyl 4-ethyl 5-oxoazepane-1,4-dicarboxylate (13) (94.5 g, 0.331 mol) in MeOH (1.3 L), NaBH4 (3.74 g, 0,099 mol) was added portionwise at 0 °C and the mixture was stirred at the same temperature for additional 1 h. The resulting solution was concentrated under vacuum. The residue was diluted with H2O (700 mL) and extracted with EtOAc (3300 mL). The combined organic extracts were washed with H2O (200 mL), brine (200 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure to give 80.1 g of crude product, that was used in the next step without further purification. To a solution of the crude 1-tert-butyl 4-ethyl 5-hydroxyazepane-1,4-dicarboxylate (80.1 g) in CH2Cl2 (1.1 L), NEt3 (117 mL, 0.834 mol) was added at 0 °C. Methanesulfonyl chloride (36.5 mL, 0.474 mol) was added dropwise while the temperature was maintained below 5 °C and the solution was stirred at rt for 4 h. The resulting mixture was treated with 10percent aq NaHCO3 (500 mL), organic phase was separated, and the aqueous phase was extracted with CH2Cl2 (3300 mL). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under reduced pressure to give 95.3 g of crude product, which was used in the next step without further purification. S4 To a solution of obtained crude 1-tert-butyl 4-ethyl 5-((methylsulfonyl)oxy)azepane-1,4-dicarboxylate (95.3 g) in THF (2.1 L), DBU (54.6 mL, 0.365 mol) was added in one portion and the reaction mixture was stirred overnight. The resulting solution was diluted with EtOAc (500 mL), washed with brine (4500 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure to give the title product. Yield: 56.8 g (64 percent); colorless oil. The compound existed as ca. 1:1 mixture of rotamers. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With methanesulfonyl chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 110℃; for 2 h; | Example 18C 1-tert-butyl 4-ethyl 2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate To a solution of EXAMPLE 18B (21 g, 73 mmol), DBU (22 g, 146 mmol) in toluene (200 mL) was added dropwise MsCl (14.56 g, 128 mmol). After the dropwise addition was completed, the mixture was stirred at 110° C. for 2 h, and cooled to room temperature, and then water (200 mL) was added to quench. The aqueous layer was extracted with EtOAc (200 mL*2). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatograph on silica gel to provide the title compound (13 g, yield: 66percent). LCMS (ESI) m/z: 270 (M+1). |
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