Structure of 5694-68-8
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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. : | 5694-68-8 |
Formula : | C4H8O3 |
M.W : | 104.10 |
SMILES Code : | OCC1OCCO1 |
MDL No. : | MFCD08062572 |
InChI Key : | ZAGUSKAXELYWCE-UHFFFAOYSA-N |
Pubchem ID : | 294864 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 22.56 |
TPSA ? Topological Polar Surface Area: Calculated from |
38.69 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.45 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
-4.74 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.65 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.05 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.89 |
Log S (ESOL):? ESOL: Topological method implemented from |
2.57 |
Solubility | 38400.0 mg/ml ; 369.0 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (Ali)? Ali: Topological method implemented from |
4.56 |
Solubility | 3740000.0 mg/ml ; 35900.0 mol/l |
Class? Solubility class: Log S scale |
Highly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
0.28 |
Solubility | 199.0 mg/ml ; 1.91 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 |
-10.3 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 |
3.0 |
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) |
2.15 |
* 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 |
---|---|---|
7.5 g (64%) | (a) 2-(2-Hydroxymethyl)-1,3-dioxolane Dowex MSA-1 (90 g, carbonate form) and 2-(2-bromoethyl)-1,3-dioxolane (18.1 g, 100 mmol) were refluxed in benzene (250 ml) for 5 hours. The resin was filtered off, washed with dichloromethane (200 ml) and methanol (500 ml). The organic solvents were evaporated and the 2-(2-hydroxyethyl)-1,3-dioxolane distilled as a colourless oil. Yield 7.5 g (64percent). B.p. 150° C. (80 mm Hg). The structure was confirmed by 1 H NMR and 13 C NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.3% | With hydrogen;palladium(II) hydroxide/carbon; In methanol; at 20℃; for 15h; | (66b) 1,3-dioxolan-2-ylmethanol To a methanol (100 ml) solution of 2-((benzyloxy)methyl)-1,3-dioxolane (3.01 g, 15.5 mmol) obtained in the step (66a) above, palladium hydroxide (20 wt. percent Pd (dry basis) on carbon, wet (water max. 50percent))(300 mg) was added and the mixture was stirred in a hydrogen atmosphere at room temperature for 15 hours. The reaction vessel was purged with nitrogen and a catalyst was removed by filtration through celite, and then, washed with methanol. The filtrate was concentrated and dried under reduced pressure to obtain the title compound (1.57 g, 97.3percent yield) as a light yellow oil. 1H NMR(400 MHz, CDCl3) deltappm; 1.89(1H, br s), 3.66-3.72(2H, m), 3.88-4.08(4H, m), 5.01(1H, t, J=3 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In water; at 20℃; for 1h; | In a four necked round-bottomed glass reactor, equipped with magnetic stirrer, thermometer, condenser maintained at -75°C (dry ice-lsopropyl alcohol) and two addition funnels, 60 g of glycol aldehyde (1.0 mol) and 62 g of ethylene glycol (1.0 mol) were loaded, followed by 10 g of 37percent HCI water solution (0.10 mol HCI) at room temperature; after 1 hour under stirring, the formation of cyclic acetal (G) was complete; the reactor was thus cooled to 0°C with an ice water bath, then a solution of 44 g (1.1 mol) of NaOH (s) and 44 ml of distilled water H2O was added in half an hour. After a slight exothermicity, at 0°C, 216 g (1.0 mmol) of (A) were slowly added. At the end of the addition, the reaction mixture was allowed to reach 20°C, and stirred for another 2 hours. The crude mixture was extracted three times with tetrahydrofuran (THF). The combined THF extracts were dehydrated with MgSO4, filtered and fractionally distilled, collecting 247 g of the partially hydrogenated ether (H) (yield 77percent mol). The aldehyde group of adduct (H) was deprotected (quantitatively) obtaining the corresponding aldehyde (J) by hydrolysis in acidic conditions (diluted HCI). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | In a four necked round-bottomed glass reactor, equipped with magnetic stirrer, thermometer, condenser maintained at -75°C (dry ice-lsopropyl alcohol) and two addition funnels, 60 g of glycol aldehyde (1.0 mol) and 62 g of ethylene glycol (1.0 mol) were loaded, followed by 10 g of 37percent HCI water solution (0.10 mol HCI) at room temperature; after 1 hour under stirring, the formation of cyclic acetal (G) was complete; the reactor was thus cooled to 0°C with an ice water bath, then a solution of 44 g (1.1 mol) of NaOH (s) and 44 ml of distilled water H2O was added in half an hour. After a slight exothermicity, at 0°C, 216 g (1.0 mmol) of (A) were slowly added. At the end of the addition, the reaction mixture was allowed to reach 20°C, and stirred for another 2 hours. The crude mixture was extracted three times with tetrahydrofuran (THF). The combined THF extracts were dehydrated with MgSO4, filtered and fractionally distilled, collecting 247 g of the partially hydrogenated ether (H) (yield 77percent mol). The aldehyde group of adduct (H) was deprotected (quantitatively) obtaining the corresponding aldehyde (J) by hydrolysis in acidic conditions (diluted HCI). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium hydride; In diethyl ether; at 0℃; for 2.5h;Inert atmosphere; | Compound 5 (296 mg, 1.0 mmol) and <strong>[5694-68-8]1,3-dioxolane-2-methanol</strong> (<strong>[5694-68-8]hydroxyacetaldehyde ethylene acetal</strong>, 150 mg, 1.44 mmol) dissolved in anhydrous diethylether (5 mL) were treated with sodium hydride (60percent, 60 mg, 1.5 mmol) under nitrogen at 0 °C. After 2.5 h workup as for 8 followed by flash chromatography (pet. ether/ethyl acetate 5:1) gave 16: 200 mg (62percent) as a yellow solid; mp 63-64 °C.1H NMR (400 MHz, CDCl3) delta=7.18 (s, 1H, Ar-OH); 5.10 (t, 1H, CH-5c); 4.78 (s, 2H, CH2-5a); 4.05-3.91 (m, 4H, OCH2-dioxolane); 3.63 (d, 2H, CH2-5b); 2.65 (m, 2H, CH2-4); 2.16, 2.10 (s, 6H, CH3-7a and -8a); 1.76 (m, 2H, CH2-3); 1.28 (s, 6H, CH3-2a, -2a'); J5b,c=3.6 Hz. EI-MS: 322 (M+). Anal. Calcd for C18H26O5(322.4): C, 67.06; H, 8.13. Found: C, 67.04; H, 8.32. |
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