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Structure of 2-(Aminooxy)ethanol
CAS No.: 3279-95-6
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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. : | 3279-95-6 |
Formula : | C2H7NO2 |
M.W : | 77.08 |
SMILES Code : | NOCCO |
MDL No. : | MFCD00517034 |
InChI Key : | WWWTWPXKLJTKPM-UHFFFAOYSA-N |
Pubchem ID : | 3014186 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225 |
Precautionary Statements: | P210-P403+P235 |
Class: | 3 |
UN#: | 1993 |
Packing Group: | Ⅲ |
Num. heavy atoms | 5 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 16.68 |
TPSA ? Topological Polar Surface Area: Calculated from |
55.48 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-1.35 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.05 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.84 |
Log S (ESOL):? ESOL: Topological method implemented from |
0.66 |
Solubility | 356.0 mg/ml ; 4.62 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
0.68 |
Solubility | 373.0 mg/ml ; 4.84 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.63 |
Solubility | 329.0 mg/ml ; 4.27 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 |
-7.73 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 |
2.0 |
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) |
2.04 |
* 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% | In ethanol; for 18h;Reflux; | A mixture of 2-(aminooxy)ethanol (3.16 g, 41.0 mmol) and paraformaldehyde (1.23 g, 41.0 mmol) in EtOH (50 ml_) was heated under reflux for 18 h. The solvent was removed under reduced pressure to afford the subtitle compound formaldehyde 0-(2-hydroxyethyl) oxime as a colourless oil (3.56 g, 97%); 1 H NMR delta: 3.57 (2H, q), 4.05-3.96 (2H, m), 4.67 (1 H, t), 6.57 (1 H, d), 7.05 (1 H, d). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With hydrazine; In methanol; at 70℃; for 1.5h; | 13b. 2-(Aminooxy)ethan-l-olH2N. / LambdaDHA solution of the product of Example 13a (15.57 g, 75.2 mmol) and hydrazine hydrate (5.4 mL, 0.11 mol) in methanol (150 mL) were heated to 70 C for 1.5 hours. After cooling to room temperature, CHCl3 (100 mL) was added to the reaction mixture. The resulting slurry was filtered and washed with CHCl3 (100 mL x 2). The filtrate was concentrated and the residue was distilled under vacuum (0.025 mmHg) at 75 to 80 C to give a colorless oil (4.54 g, 78% yield); 1H NMR (300 MHz, CDCl3) delta 3.78 (s, 4H); 13C NMR (75 MHz, CDCl3) delta 76.3, 60.7. |
73% | With methylhydrazine; In dichloromethane; at 20℃; | 2 was obtained flask 5L in step 4 (2-hydroxy - ethoxy) - isoindole-1,3-dione (555 g, 2.679 mol) was added, dissolved under stirring in methylene chloride (2.0 L), while the reaction vessel was cooled in an ice bath, methyl hydrazine (142 mL, 2.68 mol) the inner temperature was added dropwise so as not to exceed 20 C. With the progress of the reaction, a white insoluble matter has emerged. After completion of the dropwise addition, the mixture was stirred under about 15 minutes the ice bath, the precipitated insoluble substance was filtered off through a glass filter, washed white insolubles on the filter with dichloromethane (2 x 400 mL), the filtrate and washings was combined evaporated under reduced pressure. The yellow oily residue (230g) was distilled under reduced pressure (51~54 C / 2 mmHg), the objective compound as unemployed transparent liquid 2-aminooxyethanol (162g, 73%). |
28% | With hydrazine hydrate; In methanol; at 70℃; for 1.5h; | To a stirred solution of Compound 172 (29.0 g, 139.97 mmol) in MeOH (300 mL) was added hydrazine hydrate (9.63 mL, 195.96 mmol) at room temperature. The resultant solution was stirred at 70 C for 1.5 hours. The reaction mixture was cooled to room temperature and diluted with CHCI3(1 x 300 mL). The resultant slurry was filtered through Buchner funnel and washed with CHCI3(2 x 300 mL). The filtrate was concentrated, and the residue was distilled under vacuum (0.025 mmHg) at 75-80 C to give the desired alcohol, 2-(aminooxy)ethan-1-ol (Compound 173, 3.0 g,28 %), as a colorless oil. |
With hydrazine hydrate; In methanol; for 2h;Reflux; | Hydrazine monohydrate (3.96 mg, 0.124 mmol) was added to a solution of 2-(2- hydroxyethoxy)isoindoline-1 ,3-dione (produced with a similar procedure for intermediate B) (25.6 mg, 0.124 mmol) in 5 ml_ of MeOH. The solution was heated at reflux for 2 h and then cooled to rt. White precipitate was filtered off and 1 -(3-(quinolin-6-ylmethyl)- [1 ,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (41.2) (15 mg, 0.049 mmol) was added. The pH value of the solution was adjusted to 5-6 with 1 N HCI solution. The reaction solution was then stirred at rt for 2 h. Solvent was evaporated and the crude was purified by HPLC (acidic with 0.05% TFA) to give 8 mg (44.5%) of the title compound as a white TFA salt. 1H-NMR (400MHz, MeOH-Cf4) delta ppm 9.09 (s, 1 H), 8.93 (d, 1 H), 8.27 (s, 1 H), 8.16 (m, 3H), 7.98 (d, 1 H), 7.93 (m, 1 H), 4.92 (s, 2H), 4.38 (t, 2H), 3.86 (t, 2H), 2.34 (s, 3H). LC-MS (method B): [MH]+ =363.1 , tR = 2.31 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The title compound N-[5(S)-3-[3-fluoro-4-[(1alpha,5alpha,6alpha)-6-[(2-hydroxyethoxy) iminomethyl]-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide (149 mg) was prepared from N-[5(S)-3-[3-fluoro-4-[(1alpha,5alpha,6alpha)-6-formyl-3-azabicyclo[3.1.0]hexan-3-yl]phenyl]-2-oxooxazolidin-5-ylmethyl]acetamide (150 mg) and crude <strong>[3279-95-6]O-(2-hydroxyethyl)hydroxylamine</strong> (prepared from N-(2-hydroxyethoxy)phthalimide (414 mg)) in the same manner as described for EXAMPLE 66. MS (EI+) m/z: 420 (M+). |
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