Structure of 397246-14-9
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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. : | 397246-14-9 |
Formula : | C9H19NO4 |
M.W : | 205.25 |
SMILES Code : | O=C(OC(C)(C)C)N[C@H](CCO)CO |
MDL No. : | MFCD08703679 |
InChI Key : | KLRRFBSWOIUAHZ-SSDOTTSWSA-N |
Pubchem ID : | 11954482 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.89 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 3.0 |
Molar Refractivity | 52.21 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.79 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.86 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-0.02 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.25 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.12 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.46 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.64 |
Solubility | 47.2 mg/ml ; 0.23 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.19 |
Solubility | 13.4 mg/ml ; 0.0653 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.95 |
Solubility | 23.0 mg/ml ; 0.112 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 |
-7.57 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 |
0.0 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) |
2.87 |
* 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 |
---|---|---|
68% | With sodium tetrahydroborate In ethanol at 0℃; for 1.5 h; Heating / reflux | Acetyl chloride (54.6 mL, 0.75 mol) was added drop-wise into ethanol (316 mL) at 0-5 C. When the addition was completed, the ice bath was removed and the solution was allowed to stir while warming to room temperature for another 30 mins. D-aspartic acid 1 (25 g, 0.188 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 2 was obtained as a white solid (42g, 99percent) and used directly in the next step. [00469] (BOC)20 (44.7 g, 0.21mol) was added portion-wise over 10 mins to a 0 C solution of compound 1 (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 HCI (200 mL x 3). The organic layer was dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo giving compound 3 (52 g, yield 97percent) which was used directly in the next step. [00470] NaBH4 (54.4 g, 1.44 mol) was added portion-wise over 30 mins to a 0 C solution of compound 3 (52 g, 86.4 mmol) and ethanol (600 mL). The reaction mixture was extremely exothermic and great care was exercised during the addition of reducing agent. After the addition was complete, the reaction mixture was heated to reflux for 1 hour. The solution was cooled to ambient temperature and the reaction mixture solidified. The solid was broken-up to a slurry, which was then poured into brine (250 mL). The resulting mixture was filtered and the filtrate was concentrated in vacuo. The resulting residue was vigorously stirred with ether (200 mL x 5). The ether layers were successively decanted from the residue. The combined ether extracts were dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo giving compound 4 as white solid (25.2g, yield 68percent). [Note: Yield was 89percent when performed on a 25 g (compound 3) scale,] [00471] t-Butyldiphenylchlorosilane (31.9 mL, 0.123 mol) was added to a solution of compound 4 (25.2 g, 0.123 moll, diisopropylethylamine (42.8 mL, 0.245 mol), and CH2Cl2 (500 mL). The reaction solution was stirred at ambient temperature for 24 hrs. The reaction solution was then washed with 0.5 N HCI (150 mL x 3) and brine (150 mL). The organic layer was dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The resulting residue was purified by flash chromatography (silica gel, 4:1 hexanes:EtOAc) to give compound 5 (42g, yield 77percent). [Note: Yield was 85percent when performed on 15 g (compound 4) scale.] [00472] Iodine (24 g, 94.7 mmol) was added portion-wise over 15 mins to a 0 C solution of compound 5 (28 g, 63.1mmol), Ph3P (24.8 g, 94.7 mmol), imidazole (6.4g, 94.7 mmol), diethyl ether (450 mL) and acetonitrile (150mL). The ice bath was removed and the reaction solution was allowed to wann to ambient temperature over 30 mins. The reaction was judged complete by TLC analysis (4:1 hexanes:EtOAc), The reaction was quenched with water (400 mL). The layers were separated and the aqueous layer was extracted by diethyl ether (100 mL). The combined organic layers were washed with saturated aqueous Na2SO3 (100 x 2) and brine (100 mL). The organic layer was dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The resulting residue was purified by flash column chromatography (silica gel, 4:1 hexanes:EtOAc) to give compound 6 (32 g, 92percent). |
68% | With sodium tetrahydroborate In ethanol at 0℃; for 1.5 h; Heating / reflux | [00224] NaBH4 (54.4 g, 1.44 mol) was added portion- wise over 30 mins to a 00C solution of compound 19.3 (52 g, 86.4 mmol) and ethanol (600 mL). The reaction mixture was extremely exothermic and great care was exercised during the addition of reducing agent. After the addition was complete, the reaction mixture was heated to reflux for 1 hour. The solution was cooled to ambient temperature and the reaction mixture solidified. The solid was broken-up to a slurry, which was then poured into brine (250 mL). The resulting mixture was filtered and the filtrate was concentrated in vacuo. The resulting residue was vigorously stirred with ether (200 mL x 5). The ether layers were successively decanted from the residue. The combined ether extracts were dried over magnesium sulfate, filtered, and the filtrate was concentrated in vacuo giving compound 19.4 as white solid (25.2g, yield 68percent). |
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