Structure of 2-(Benzyloxy)ethanol
CAS No.: 622-08-2
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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. : | 622-08-2 |
Formula : | C9H12O2 |
M.W : | 152.19 |
SMILES Code : | OCCOCC1=CC=CC=C1 |
MDL No. : | MFCD00002868 |
InChI Key : | CUZKCNWZBXLAJX-UHFFFAOYSA-N |
Pubchem ID : | 12141 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.33 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 43.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
29.46 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.92 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.11 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.04 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.87 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.44 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.62 |
Solubility | 3.63 mg/ml ; 0.0238 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.32 |
Solubility | 7.26 mg/ml ; 0.0477 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.76 |
Solubility | 0.264 mg/ml ; 0.00174 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) |
Yes |
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 |
-6.44 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) |
1.45 |
* 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 pyridine; | Preparation 1 A mixture of chlorodiphenylacetyl chloride (20 g), <strong>[13220-33-2]1-methyl-3-pyrrolidinol</strong> (7.6 g), and pyridine (35 g) is kept at room temperature for two hours. After adding 45 g of 2-benzyloxyethanol, the mixture is refluxed gently for 18 hours. Excess pyridine and benzyloxyethanol are distilled off under reduced pressure, the residue is dissolved in ether and washed twice with water. The organic phase is dried over magnesium sulfate (MgSO4), filtered and the filtrate evaporated to dryness. Chromatography of the residue on the silica gel with ethyl acetate-hexane-triethylamine (50:50:1) as eluent affords 18 g of 1-methyl-3-[2,2-diphenyl-2-(2-benzyloxyethoxy)acetoxy]pyrrolidine as an oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 25℃; for 6h; | 11231] To a solution of 643-1 (1.5 g, 6.9 mmol) in DMF (20 mL) was added 2- benzyloxyl ethanol (6.3 g, 41 mmol) at 25 °C. The solution wras stirred for 6 h and then poured into 0 (20 mL). The mixture was extracted with EA (2 x 40 mL). The combined organic phase was washed with brine, dried over anhydrous Na^SC^ and concentrated under reduced pressure. The residue was purified by column chromatography using 5-10percent EA in PE as the eluent to give a mixture of 643-2 and 643-2 A ( 1 .50 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11231] To a solution of 643-1 (1.5 g, 6.9 mmol) in DMF (20 mL) was added 2- benzyloxyl ethanol (6.3 g, 41 mmol) at 25 °C. The solution wras stirred for 6 h and then poured into 0 (20 mL). The mixture was extracted with EA (2 x 40 mL). The combined organic phase was washed with brine, dried over anhydrous Na^SC^ and concentrated under reduced pressure. The residue was purified by column chromatography using 5-10percent EA in PE as the eluent to give a mixture of 643-2 and 643-2 A ( 1 .50 g). [1232] To a solution of 643-2A and 643-2 A (1.50 g. crude mixture) in EtOI I/I I20 (20/1 OmL) were added Fe ( 1 .5 g. 26.7 mmol) and NH4C1 (1 .5 g, 28 mmol) at 25 °C. The solution was heated to 80 °C and stirred for 2 h. The mixture was filtered, and the filtrate was concentrated to give a mixture of 643-3 and 643-3A ( 1.20 g, crude). The products were used for the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11231] To a solution of 643-1 (1.5 g, 6.9 mmol) in DMF (20 mL) was added 2- benzyloxyl ethanol (6.3 g, 41 mmol) at 25 °C. The solution wras stirred for 6 h and then poured into 0 (20 mL). The mixture was extracted with EA (2 x 40 mL). The combined organic phase was washed with brine, dried over anhydrous Na^SC^ and concentrated under reduced pressure. The residue was purified by column chromatography using 5-10percent EA in PE as the eluent to give a mixture of 643-2 and 643-2 A ( 1 .50 g). [1232] To a solution of 643-2A and 643-2 A (1.50 g. crude mixture) in EtOI I/I I20 (20/1 OmL) were added Fe ( 1 .5 g. 26.7 mmol) and NH4C1 (1 .5 g, 28 mmol) at 25 °C. The solution was heated to 80 °C and stirred for 2 h. The mixture was filtered, and the filtrate was concentrated to give a mixture of 643-3 and 643-3A ( 1.20 g, crude). The products were used for the next step without further purification.[1233] A mixture of 643-3 and 643-3A (1.2 g, crude) in H2S04/H20 (1 : 1 ) (l OmL) was cooled to -5 °C. NaN02 (376 mg, 5.45 mmol) was added in portions at -5 °C. The solution wras stirred at -5 °C for 0.5 h. The solution was heated to 120 °C. After stirring 0.5 h at 120 °C, the solution was poured into ice water (20 mL) and extracted with EA (2 x 20 mL). The organic phase was concentrated at low pressure. The residue was purified by chromatography to give 643-4 (0.3 g, crude). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23.74% | With caesium carbonate; copper dichloride; at 130℃;Inert atmosphere; | To a stirred mixture of 4-bromo-l-methyl-lH-pyrazole-5-carboxylic acid (60 g, 292.67 mmol, 1 equiv) in 2-(benzyloxy)ethan-l-ol (300 mL) were added CS2CO3 (286.1 g, 878.00 mmol, 3.00 equiv) and CuCh (3.9 g, 29.27 mmol, 0.10 equiv). The resulting mixture was stirred for overnight at 130 C under nitrogen atmosphere. The reaction was quenched with water and extracted with EtOAc. The aqueous phase was acidified to pH 2 with cone. HC1 and the resulting mixture was extracted with EtOAc. The combined organic layers were concentrated under reduced pressure. The residue was purified by reverse flashchromatography under the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in water, 0% to 35% gradient in 25 min; detector, UV 254 nm to give (19.2 g, 23.74%) of the title compound as a white solid. LC-MS: (ES, m/z): [M+H]+277. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
17% | With potassium carbonate; copper(ll) bromide; at 100℃;Inert atmosphere; | To a stirred solution of <strong>[64224-60-8]5-bromopyrimidine-4-carboxylic acid</strong> (4.3 g, 21.183 mmol, 1 equiv) and 2-(benzyloxy)ethan-l-ol (25 mL) were added K2CO3 (8.78 g, 63.548 mmol, 3 equiv) and CuBr2 (0.95 g, 4.237 mmol, 0.2 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred for overnight at 100 C under nitrogen atmosphere. The mixture was acidified to pH 5 with HC1 (aq.) and extracted with EA. The residue was purified by silica gel column chromatography, eluted with CH2CI2 / MeOH (10: 1) to afford PH-IDE-0637-1 (1.0 g, 17 %) as a white solid. |
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