Structure of H-D-Asp(OEt)-OEt·HCl
CAS No.: 112018-26-5
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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. : | 112018-26-5 |
Formula : | C8H16ClNO4 |
M.W : | 225.67 |
SMILES Code : | O=C(OCC)[C@H](N)CC(OCC)=O.[H]Cl |
MDL No. : | MFCD11225843 |
InChI Key : | AJOXZAAREAYBQR-FYZOBXCZSA-N |
Pubchem ID : | 12416467 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.75 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.81 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.62 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 |
0.6 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.63 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.42 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.24 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.38 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.16 |
Solubility | 15.8 mg/ml ; 0.07 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.82 |
Solubility | 3.38 mg/ml ; 0.015 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.94 |
Solubility | 26.0 mg/ml ; 0.115 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 |
-7.25 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.63 |
* 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 |
---|---|---|
97% | With triethylamine; In 1,4-dioxane; water; at 0 - 20℃; for 2.33333h; | [00223] (Boc)2O (44.7 g, 0.21mol) was added portion-wise over 10 min to a 0 0C solution of compound 19.2 (42 g, 0.19 mol), trimethyl amine (51.9 mL, 0.37 mol), dioxane (140 mL) and water (56 mL). After another 10 min, the ice bath was removed and the reaction mixture was stirred while warming to room temperature for another 2 hours. The reaction mixture was diluted in ethyl acetate (150 mL) and washed with 0.5 N HCl (200 mL x 3). The organic layer was dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo giving compound 19.3 (52 g, yield 97%) which was used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | [00222] Acetyl chloride (54.6 mL, 0.75 mol) was added drop- wise into ethanol (316 mL) at 0-5 0C. When the addition was completed, the ice bath was removed and the solution allowed to stir while warming to room temperature for another 30 min. D-aspartic acid 19.1 (25 g, 0.188 <n="77"/>mol) was then added. The reaction mixture was refluxed for 2 hours. The reaction solution was then concentrated in vacuo and placed under high vacuum (0.4 mm Hg) overnight. Compound 19.2 was obtained as a white solid (42 g, 99%) and used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 20℃; for 25h;Cooling with ice; | General procedure: AAEs were synthesized using a slight modification of an establishedmethod (Furukawa et al., 2016). Briefly, a suspension of 2.0 g of anamino acid in 20 mL of the required alcohol (e.g., methanol for methylester, ethanol for ethyl ester) was stirred vigorously in an ice bath.Then, thionyl chloride (mole ratio of thionyl chloride: aminoacid=1.5:1) was added dropwise to the slurry, and the mixture waskept on ice for 1 h. The resultant solution was stirred thoroughly for24 h at room temperature (Scheme 1a) and then concentrated underreduced pressure after completion of the reaction. The oily residue wasdissolved in alcohol (10 mL) and the solvent was evaporated underreduced pressure to yield the AAE hydrochloride salt. Then, 10 mL ofdistilled water was added to the solution, followed by neutralizationwith ammonia solution (mole ratio of ammonia: AAE salt=2:1). Diethylether (50 mL) was added, and the solution was stirred for 2 h atroom temperature (Scheme 1b). The organic layer was extracted andconcentrated under reduced pressure to yield the AAE. The yields of allthe synthesized compounds were ?72.0% (Table S1). All the synthesizedcompounds were characterized by 1H and 13C nuclear magneticresonance spectroscopy (NMR) and elemental analysis to check theirstructures and purities. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; In diethyl ether; water; at 20℃; for 2h; | General procedure: AAEs were synthesized using a slight modification of an establishedmethod (Furukawa et al., 2016). Briefly, a suspension of 2.0 g of anamino acid in 20 mL of the required alcohol (e.g., methanol for methylester, ethanol for ethyl ester) was stirred vigorously in an ice bath.Then, thionyl chloride (mole ratio of thionyl chloride: aminoacid=1.5:1) was added dropwise to the slurry, and the mixture waskept on ice for 1 h. The resultant solution was stirred thoroughly for24 h at room temperature (Scheme 1a) and then concentrated underreduced pressure after completion of the reaction. The oily residue wasdissolved in alcohol (10 mL) and the solvent was evaporated underreduced pressure to yield the AAE hydrochloride salt. Then, 10 mL ofdistilled water was added to the solution, followed by neutralizationwith ammonia solution (mole ratio of ammonia: AAE salt=2:1). Diethylether (50 mL) was added, and the solution was stirred for 2 h atroom temperature (Scheme 1b). The organic layer was extracted andconcentrated under reduced pressure to yield the AAE. The yields of allthe synthesized compounds were ?72.0% (Table S1). All the synthesizedcompounds were characterized by 1H and 13C nuclear magneticresonance spectroscopy (NMR) and elemental analysis to check theirstructures and purities. |