Structure of 1010814-94-4
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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. : | 1010814-94-4 |
Formula : | C16H27NO5 |
M.W : | 313.39 |
SMILES Code : | O=C(N1CC(CC(OC(C)(C)C)=O)C(CC1)=O)OC(C)(C)C |
MDL No. : | MFCD11111810 |
InChI Key : | ALIVCUSTZCGWKQ-UHFFFAOYSA-N |
Pubchem ID : | 49759529 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 22 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.81 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 86.96 |
TPSA ? Topological Polar Surface Area: Calculated from |
72.91 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 |
1.41 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.16 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.21 |
Solubility | 1.94 mg/ml ; 0.00618 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.55 |
Solubility | 0.893 mg/ml ; 0.00285 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.45 |
Solubility | 1.11 mg/ml ; 0.00355 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 |
-7.21 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) |
3.41 |
* 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 |
---|---|---|
50.6% | To a solution of diisopropylamine (13.5 ml, 96 mmol) in THF (300 ml) at -78C was added dropwise n-BuLi (2.5M in Hex, 32 ml). The mixture was warmed to -100C and re-cooled to -78C. A solution of 4-oxo-piperidine-l-carboxylic acid tert-butyl ester (10 g, 50 mmol) in THF (50 ml) was then added dropwise and the mixture stirred at -78C for another 15 min. A solution of tert-butyl bromoacetate (12.6 ml, 85 mmol) in THF (30 ml) and HMPT (5 ml) was then added dropwise and the mixture stirred at -78C for 4 h and then gradually warmed to rt. The mixture was taken up in sat. aq. NH4Cl and extracted with EA. The yield after work up and chromatography (eluent Hex/EA 4:1) was 7.6 g (50.6%; yellowish oil).1H NMR (CDCl3) delta: 4.40-4.20 (m, 2H); 3.25-3.15 (m, IH); 3.00-2.80 (m, 2H); 2.70-2.40 (m, 3H); 2.30-2.10 (m, IH); 1.51 (s, 9H), 1.46 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Methyltriphenylphosphonium bromide (8.5 g, 23.9 mmol) was suspended in THF (23 ml) and treated with KOtBu (2.7 g, 23.9 mmol). The resulting yellow suspension was stirred at rt for 1 h. A solution of the intermediate 7.i (3.0 g, 9.6 mmol) in THF was added dropwise and the mixture was stirred at rt for 2 h, taken up in water and diluted with ether. The yield after work up and chromatography (Hex:EA 9:1) was 1.8 g (60%; colourless oil). 1H NMR (CDCl3) delta: 4.80 (s, IH); 4.75 (s, IH); 4.60-4.20 (m, 4H); 2.80-2.60 (m, IH); 2.50-2.25 (m, 3H); 2.25-2.10 (m, IH); 1.48 (s, 9H); 1.46 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a solution of diisopropylamine (7.41 g, 73.2 mmol) in dry tetrahydrofuran (150 mL) was added n-BuLi (2.5 M, 16 mL) dropwise at -70 C under nitrogen. The resultant mixture was warmed to -10 C and stirred for 30 min. The mixture was cooled to -70 C, and a solution of tert-butyl 4-oxopiperidine-1-carboxylate (5.00 g, 25.1 mmol) in dry tetrahydrofuran (20.0 mL) was added dropwise and stirred for 30 min. Then, a solution of tert-butyl 2-bromoacetate (4.89 g, 25.1 mmol) in tetrahydrofuran (20.0 mL) was added dropwise, followed by hexamethylphosphoramide (HMPA) (1.80 g, 11.0 mmol). On completion, to the mixture was added water (10 mL), and the solution was extracted with ethyl acetate (3 x 50 mL). The combined ethyl acetate phase was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether:ethyl acetate = 0:1 to 100:1) to give the title compound. 1H NMR (300 MHz, CDCl3) delta = 4.22 - 4.03 (m, 1H), 3.65 (t, J = 6.0 Hz, 2H), 2.83 (s, 1H), 2.57 - 2.33 (m, 4H), 2.32 - 2.06 (m, 1H), 1.43 (s, 9H), 1.38 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate; sodium cyanoborohydride; In tetrahydrofuran; at 20℃; for 16h;Molecular sieve; | To a mixture of (±)-tert-butyl 3-(2-tert-butoxy-2-oxo-ethyl)-4-oxo-piperidine-1- carboxylate (2.00 g, 6.38 mmol) in tetrahydrofuran (20.0 mL) was added ammonium acetate (1.48 g, 19.1 mmol), followed by 4A MS (500 mg), and sodium cyanotrihydroborate (1.20 g, 19.1 mmol) in one portion at 20 C. The mixture was stirred at 20 C for 16 hrs. On completion, to the mixture was added water (30 mL) and the solution was extracted with dichloromethane (3 x 30 mL). The combined dichloromethane phase was dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 10:1 to dichloromethane:methanol = 20:1) to give the title compound (crude).1H NMR (400 MHz, DMSO-d6) delta = 3.90 - 3.72 (m, 2H), 3.41 - 3.31 (m, 1H), 3.08 - 2.74 (m, 3H), 2.37 - 2.24 (m, 1H), 1.87 - 1.84 (m, 1H), 1.63 - 1.39 (m, 19H). |
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