Structure of 279227-92-8
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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. : | 279227-92-8 |
Formula : | C11H21ClN2O4 |
M.W : | 280.75 |
SMILES Code : | O=C(N1[C@@H](C(OC)=O)CNCC1)OC(C)(C)C.[H]Cl |
MDL No. : | MFCD07366808 |
InChI Key : | MESGHYLTRXYTHM-DDWIOCJRSA-N |
Pubchem ID : | 45072201 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.82 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 76.37 |
TPSA ? Topological Polar Surface Area: Calculated from |
67.87 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.21 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.41 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.5 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.45 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.01 |
Solubility | 2.73 mg/ml ; 0.00971 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.23 |
Solubility | 1.65 mg/ml ; 0.00586 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.13 |
Solubility | 20.9 mg/ml ; 0.0743 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 |
-7.15 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) |
3.08 |
* 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 |
---|---|---|
PREPARATIVE EXAMPLE 3; 1 ,1-Dimethyl-4-(8-chloro-5,11-dihvdro-ϖibenzoxepinor4,3-bipyridin-11-yl)-2(RV (methoxycarbonyl)piperazinecarboxylate The tricyclic alcohol (Biorg. & Med. Chem. Lett. 2521 , 1998) (7.01 gm, 28.3 mmol) was dissolved in toluene (100 mL) and SOCb (4 mL) was added while stirring under a dry N2 atmosphere. After 4 hrs, the mixture was evaporated to give a gum which was extracted with EtOAc and washed with 10% NaOH. The organics were dried over MgSO4, filtered and concentrated under reduced pressure to give a foamy solid. The resulting chloro-trycyclic compound was dissolved in dry DMF (100 mL) and the title compound from Preparative Example 2 (7. 94 gm, 28.29 mmol) was added followed by 4-methyl morpholine 15.54 mL, 141 mmol) and the mixture was stirred at room temperature under N2. After 24 hrs, the reaction mixture was concentrated and the residue dissolved in EtOAc and washed with brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure to give the title compond (9.5 g) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; hydrogen;palladium on activated charcoal; In methanol; water; for 18.0h; | PREPARATIVE EXAMPLE 2; The title compound from Preparative Example 1 (1.85 gm) was dissolved in MeOH (25 mL) and 1 N HCI (0.5 mL) in a hydrogenation vessel. The vessel was flushed with N2 and 10% Pd/C (0.38 gm, 50% weight with water) was added. The mixture was hydrogenated at 55 psi of H2 for 18 hours. When the reaction was complete (TLC, 25% EtOAc/Hexane) the catalyst was filtered off and the filtrate was evaporated to dryness to give the title compound (1.3 gm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium carbonate; In 1,4-dioxane; water; for 18.0h; | Synthesis of (R)-Piperazine-l,2,4-tricarboxylic acid 1,4-di-tert-butyl ester 2-methyl ester [A037] To a stirred suspension of (R)-l-N-Boc-piperazine-2-carboxylic acid methyl ester hydrochloride (2 g, 7.12 mmol) and a2CC>3 (2.26 g, 21.4 mmol) in dioxane (16ml) and water (4 ml) at 0 C was added Di-tert-butyl-dicarbonate (1.55 g, 7.12 mmol). After 18 hours all solvents were removed in vacuo and the resulting residue partitioned between DCM and water. The organic phase was collected and evaporated to give a colourless oil. Purification by column chromatography (0-30% EtOAc:cyclohexane) gave the title compound [A037] as a white powder (2.33 g, 95%). 1H-NMR (1H, 300MHz, CDC13): 5.30 (1H, s), 4.72 (1H, s, br), 4.54 (1H, t, br), 4.08-3.80 (1H, m), 3.73 (3H, s), 3.27-2.73 (3H, m), 1.44 (18H, s). |
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