Structure of 783350-37-8
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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. : | 783350-37-8 |
Formula : | C10H17NO5 |
M.W : | 231.25 |
SMILES Code : | O=C([C@H]1N(C(OC(C)(C)C)=O)CCOC1)O |
MDL No. : | MFCD04114904 |
InChI Key : | KVXXEKIGMOEPSA-ZETCQYMHSA-N |
Pubchem ID : | 1512537 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.8 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 59.45 |
TPSA ? Topological Polar Surface Area: Calculated from |
76.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.96 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.37 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.07 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.24 |
Solubility | 13.2 mg/ml ; 0.0572 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.53 |
Solubility | 6.78 mg/ml ; 0.0293 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.12 |
Solubility | 177.0 mg/ml ; 0.764 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 |
-7.45 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 |
0.56 |
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) |
3.13 |
* 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 |
---|---|---|
With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; | INTERMEDIATE 33: MORPHOLINE-3 (S), 4-DICARBOXYLIC ACID 4- tert-butyl ester [00157] A suspension of morpholine-3 (S)-CARBOXYLIC acid (2.00 g, 15.3 mmol) in DMF (75 ml) was stirred at RT. Triethylamine (7.47 ml, 53.6 mmol) and di-tert-butyl dicarbonate (BOC20, 4.02 g, 18.4 mmol) were added. The suspension was stirred at RT for one hour, during which time the reaction formed a clear yellow solution. The solution was concentrated to a reduced volume (-25 ml) and diluted with water (15 ml) and IN HC1 (15 ml). The mixture was poured into a separatory funnel, diluted further with water (100 ml) and brine (100 ml), and extracted with ET20 (3 x 100 ml). The organic layer was washed with brine, dried, filtered and concentrated to yield a white solid. The solid, which contained excess BOC20, was dissolved in ET20 (500 ml) and extracted with IN NaOH (3 x 100 ml). The aqueous layer was acidified with 6N HC1 to approximately a pH of 2, then extracted quickly with ET20 (3 x 100 ml). The ET20 layer was dried, filtered and concentrated to yield white solid (3.07 g). H-NMR (300 MHz, DMSO-d6): 5 12.95 (br s, 1); 4.34-4. 30 (m, 1); 4.18-4. 10 (m, 1); 3.83-3. 74 (m, 1); 3.59-3. 51 (m, 2); 3.39-3. 32 (m, 1); 3.21-2. 95 (m, 1); 1.41-1. 36 (m, 9). NH40Ac standard conditions. ELSD Rf = 1.08 min. M-H = 230. | |
With triethylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 1h; | Intermediate 33: morpholine-3(S), 4-dicarboxylic acid 4-tert-butyl ester A suspension of <strong>[106825-79-0]morpholine-3(S)-carboxylic acid</strong> (2.00 g, 15.3 mmol) in DMF (75 ml) was stirred at RT. Triethylamine (7.47 ml, 53.6 mmol) and di-tert-butyl dicarbonate (BOC2O, 4.02 g, 18.4 mmol) were added. The suspension was stirred at RT for one hour, during which time the reaction formed a clear yellow solution. The solution was concentrated to a reduced volume (25 ml) and diluted with water (15 ml) and 1N HCl (15 ml). The mixture was poured into a separatory funnel, diluted further with water (100 ml) and brine (100 ml), and extracted with Et2O (3*100 ml). The organic layer was washed with brine, dried, filtered and concentrated to yield a white solid. The solid, which contained excess BOC2O, was dissolved in Et2O (500 ml) and extracted with 1N NaOH (3*100 ml). The aqueous layer was acidified with 6N HCl to approximately a pH of 2, then extracted quickly with Et2O (3*100 ml). The Et2O layer was dried, filtered and concentrated to yield white solid (3.07 g). 1H-NMR (300 MHz, DMSO-d6): delta 12.95 (br s, 1); 4.34-4.30 (m, 1); 4.18-4.10 (m, 1); 3.83-3.74 (m, 1); 3.59-3.51 (m, 2); 3.39-3.32 (m, 1); 3.21-2.95 (m, 1); 1.41-1.36 (m, 9). NH4OAc standard conditions. ELSD Rf=1.08 min. M-H=230. | |
With sodium hydrogencarbonate; In 1,4-dioxane; water; at 20℃; for 16h; | A mixture of (S)morphoine-3-carboxyic acid (1.0 g, 7.63 mmo) and Boc2O (1.77 m, 763 mmoD in 10% NaHCO3 so?ution in water (10 m, 7.63 mmofl and 1,4dioxane (10 m) was stirred at RT for 16h. Water and AcOEt were added to mixture and phases were separated. The aqueous ayer was acidified to pH 34 with IM aqueous citric acid (12 m) and extracted 3 times with AcOEt. The organic ayer was washed with brine, dried over a phase separator cartridge (ST), the sovent was evaporated and the residue dried under vacuum to afford (S)-4(tert-butoxycarbony)morphoHne-3-carboxyHc acid Mz = 232 [M+Hj+, Rt = 070 mm (UPLC Method B2), 1H NMR (400 MHz. DMSO-d5) 6ppm: 12.94 (bs, IH), 4.32 (dd, IH), 4.15 (dd, IH), 3.79 (ddd, IH), 3.58-3.51 (m, 2H), 3.39-2.97 (m, 2H), 1.38 (d, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trifluoroacetic acid; In dichloromethane; at 20℃; for 0.5h; | (S)-4-(tert-Butoxycarbonyl)morpholine-3-carboxylic acid (4.60 g, 20.0 mmol)Add to dichloromethane (20 mL),Add trifluoroacetic acid (20 mL) and stir at room temperature.After 30 minutes, the reaction is completed.The reaction mixture was dried to give the title compound. |
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