Structure of 2,2'-(Benzylimino)diethanol
CAS No.: 101-32-6
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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. : | 101-32-6 |
Formula : | C11H17NO2 |
M.W : | 195.26 |
SMILES Code : | OCCN(CCO)CC1=CC=CC=C1 |
MDL No. : | MFCD00020587 |
InChI Key : | MIZIOHLLYXVEHJ-UHFFFAOYSA-N |
Pubchem ID : | 7553 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H319 |
Precautionary Statements: | P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.45 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 55.86 |
TPSA ? Topological Polar Surface Area: Calculated from |
43.7 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.86 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.23 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.07 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.51 |
Solubility | 5.99 mg/ml ; 0.0307 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.36 |
Solubility | 8.5 mg/ml ; 0.0435 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.61 |
Solubility | 0.478 mg/ml ; 0.00245 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 |
-6.88 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 |
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) |
1.06 |
* 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 |
---|---|---|
54.6% | With phosphorus tribromide; In toluene; at 0℃; for 6h;Inert atmosphere; Reflux; | A mixture of compound O-1 (12.10 g, 115.1 mmol), benzyl bromide (13.70 mL, 115.3 mmol) and potassium carbonate (31.81 g, 230.2 mmol) in acetone (120 mL) was refluxed for 18 hours, cooled to rt and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (DCM/MeOH (v/v) = 20/1) to give compound O-2 as pale yellow liquid (16.39 g, 72.9%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3): delta 7.36-7.23 (m, 5H), 3.70 (s, 2H), 3.62 (t, J = 5.3 Hz, 4H), 2.72 (t, J = 5.3 Hz, 4H), 2.48 (brs, 2H). [0555] To a solution of compound O-2 (14.60 g, 74.77 mmol) in toluene (140 mL) was added phosphorus tribromide (21.1 mL, 224.5 mmol) dropwise at 0 C under N2. At the end of the addition, the mixture was refluxed for 6 hours, cooled to rt, quenched with ice water (400 mL) and filtered. The filtrate was washed with NaOH solution and extracted with DCM (100 mL x 3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/EtOAc (v/v) = 10/1) to give the title compound 32-1 as colorless oil (13.30 g, 54.6%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3): delta 7.36-7.25 (m, 5H), 3.73 (s, 2H), 3.34 (t, J = 7.3 Hz, 4H), 2.98 (t, J = 7.3 Hz, 4H). |
54.6% | With phosphorus tribromide; In toluene; at 0℃; for 6h;Inert atmosphere; Reflux; | To a solution of compound O-2 (14.60 g, 74.77 mmol) in toluene (140 mL) was added phosphorus tribromide(21.1 mL, 224.5 mmol) dropwise at 0 C under N2. At the end of the addition, the mixture was refluxed for 6 hours, cooledto rt, quenched with ice water (400 mL) and filtered. The filtrate was washed with NaOH solution and extracted withDCM (100 mL x 3). The combined organic phases were dried over anhydrous Na2SO4 and concentrated in vacuo. Theresidue was purified by silica gel column chromatography (hexane/EtOAc (v/v) = 10/1) to give the title compound 32-1as colorless oil (13.30 g, 54.6%). The compound was characterized by the following spectroscopic data:1H NMR (400 MHz, CDCl3): delta 7.36-7.25 (m, 5H), 3.73 (s, 2H), 3.34 (t, J = 7.3 Hz, 4H), 2.98 (t, J = 7.3 Hz, 4H). |
18% | With phosphorus tribromide; In dichloromethane; at 0 - 20℃; for 8h; | Into a 500-mL round-bottom flask was placed 2,2'-(benzylazanediyl)diethanol (11.3 g, 57.9 mmol, 1 equiv) and CH2C12 (100 mL). This was followed by the dropwise addition of phosphorus tribromide (34.6 g, 128 mmol, 2.2 equiv) at 0 C. The resulting solution was stirred for 8 h at room temperature. The reaction was then quenched by the addition of 80 mL of ice-water. The pH value of the solution was adjusted to 7 with sat. aq. Na2C03 solution. The resulting solution was extracted with 3x80 mL of CH2C12. The combined organic layers were dried over anhydrous Na2S04, filtered, and concentrated under vacuum. The residue was purified by normal phase chromatography on silica gel using CH2Cl2/petroleum ether (1 :3). The collected fractions were concentrated under vacuum to afford 3.3 g (18% yield) of the title compound as yellow oil. 1H MR (400 MHz, CDC13) delta (ppm): 7.34-7.27 (m, 5H), 3.73 (s, 2H), 3.43 (t, J= 7.2 Hz, 4H), 2.98 (t, J= 7.2 Hz, 1H). |
41.58 g | With phosphorus tribromide; In toluene; at 0 - 105℃; for 16h; | To a 0 C solution of 2,2?-(benzylazanediyl)bis(ethan-l-ol) (30.66 g, 0.16 mol) intoluene (300 mL) was added tribromophosphane (69.13 g, 0.26 mol) dropwise. The resultingmixture was stirred at 105 C for 16 h. After cooling to RT, the volatiles were removed under reduce pressure. The residue was diluted with water (300 mL), and the pH value was adjusted to 9with NaOH. The resulting mixture was extracted with EA (3 x 150 mL), the organic layers combined, dried over anhydrous Na2504 and filtered. The filtrate was concentrated under reducedpressure to give N-benzyl-2-bromo-N-(2-bromoethyl) ethan-1-amine (41.58 g) which was used in next step without any further purification. MS: m/z 320 (M+H). |
41.58 g | With phosphorus tribromide; In toluene; at 0 - 105℃; for 15h; | N-Benzyldiethanolamine (30.66 g, 0.16 mol) in toluene (300 mL) at 0 CPhosphorus tribromide (69.13 g, 0.26 mol) was added dropwise to the solution. The system was heated to 105 C and stirred for 16 h.After cooling to RT, the volatiles were removed under reduced pressure. The residue was diluted with water (300 mL) and the pH was adjusted to 9 with NaOH.The system was extracted with EA (3×150 mL).The filtrate was concentrated under reduced pressure to give N-benzyl-2-bromo-N-(2-bromoethyl)ethane-l-amine (41.58 g).Used directly in the next step without any further purification. |
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