Structure of 82353-56-8
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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. : | 82353-56-8 |
Formula : | C8H15NO3 |
M.W : | 173.21 |
SMILES Code : | O=C(OC(C)(C)C)N[C@H](C)C=O |
MDL No. : | MFCD00274183 |
InChI Key : | OEQRZPWMXXJEKU-ZCFIWIBFSA-N |
Pubchem ID : | 10910049 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.28 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.4 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.9 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.1 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.53 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.51 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.98 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.13 |
Solubility | 13.0 mg/ml ; 0.0749 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.61 |
Solubility | 4.28 mg/ml ; 0.0247 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.21 |
Solubility | 10.6 mg/ml ; 0.0614 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 |
-6.75 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 |
1.0 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) |
2.3 |
* 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 |
---|---|---|
85% | Example 46(1-Methyl-2-oxo-ethyl)-carbamic acid tert-butyl ester The title compound from Example 45 (3.53 g, 17.4 mmol) was dissolved in toluene (35 mL) at -78 C. and DIBAL-H (26.6 mL, 39.9 mmol) was added dropwise over 1 hour. Methanol (70 mL) was added to the reaction over 10 min. at -78 C. The reaction was moved to an ice bath and 10% w/v citric acid in water (250 mL) was added and the reaction was allowed to stir for 1 hour. The reaction was extracted with portions of ethyl acetate and the organic extracts were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the title compound (2.57 g, 85%) as a white semi-solid.1H NMR (300 MHz, CDCl3): delta (ppm) 9.51 (s, 1H), 5.21 (broad s, 1H), 4.24 (broad s, 1H), 1.53 (s, 9H), 1.35 (d, 3H). | |
82% | Step 1: (R)-tert-butyl 1-oxopropan-2-ylcarbamateTo a cooled solution of <strong>[91103-47-8](R)-methyl 2-(tert-butoxycarbonylamino)propanoate</strong> (40.0 g, 98.0 mmol) in DCM (200 mL) at -78 C. was added diisobutylaluminum hydride (208 mL, 1.0 M in THF) dropwise over 30 min. The reaction mixture was stirred at -78 C. for 1.5 h then quenched with water (50 mL). After warmed to rt, the white precipitate was removed by filtration over Celite. The organic layer was then washed with brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography (petroleum ether: EtOAc, 10:1) to give (R)-tert-butyl 1-oxopropan-2-ylcarbamate (28.0 g, 82%). 1H NMR (DMSO-d6, 400 MHz) delta 9.43 (s, 1H), 7.33 (d, J=6.0 Hz, 1H), 3.85 (m, 1H), 1.39 (s, 9H), 1.12 (d, J=7.2 Hz, 3H). | |
65% | With diisobutylaluminium hydride; In toluene; at -78℃; for 2h; | EXAMPLE 49; (R)-5-Chloro-thiophene-2-carboxylic acid (1 - {3-[4-(N,N-dimethyl-carbamimidoyl)-phenyl]- isoxazol-5-yl}-ethyl)-amide; Step l :; [0553] Methyl ester 8 (4.03 g, 19.9 mmol) was diluted with 40 mL of toluene and cooled to -780C. Diisobutylaluminum hydride in toluene (26 mL, 40 mmol) was added slowly to the precooled mixture down the side of the flask. The reaction was stirred at -780C for two hours at which time it was treated slowly with ca. 5 mL of methanol precooled to -780C (vigorous reaction). The mixture was then warmed to it and partitioned with saturated sodium potassium tartrate and ethyl acetate. The layers were separated, the organic phase was extracted with ethyl acetate and the combined organic layers were dried over MgSO4. After filtration and concentration in vacuo the crude material was purified by filtration through a short plug of silica gel eluted with dichloromethane affording the aldehyde 9 as a colorless oil (2.23g, 65%). 1H NMR (DMSO-J6, 400 MHz): delta 9.38 (s, IH), delta 7.30 (d, IH), delta 3.79 (m, IH), delta 1.31 (s, 9H), 1.06 (d, 3H). |
With diisobutylaluminium hydride; In toluene; at -78℃; for 2h; | To a stirred solution of (S)-methyl 2-(tert-butoxycarbonylamino)propanoate (3.87 g, 19 mmol) in dry toluene (10 ml) was slowly added DIBAL-H (1.0 M in toluene solution; 24.8 ml, 24.8 mmol) at -78C. After stirring of the mixture at -78C for 2 h, excess of DIBAL-H was quenched with 1.5N HCl (5 ml). The resulting mixture was filtered and the organic layer of the filtrate was washed with saturated NaHCO3 aq and water, dried over with anhydrous MgSO4, and solvent was removed in vacuo. The residue was purified by silica gel column chromatography to give compound (1.74 g) in 53% yield. |
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