Structure of 5464-28-8
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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. : | 5464-28-8 |
Formula : | C4H8O3 |
M.W : | 104.10 |
SMILES Code : | OCC1OCOC1 |
MDL No. : | MFCD00003218 |
InChI Key : | BOHGAOWOIJMTPZ-UHFFFAOYSA-N |
Pubchem ID : | 21618 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H227-H319 |
Precautionary Statements: | 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 |
1.39 |
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 |
-0.9 |
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) |
2.89 |
* 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 |
---|---|---|
95.6% | With dihydrogen peroxide; nitric acid; cetyltrimethylammonim bromide; ferric nitrate; In water; at 80℃; for 5.0h; | Will be 920g of glycerin,990gParaformaldehyde and20 g of the supported solid super acid catalyst prepared in Example 2 was addedIn the reaction device, the reaction is heated to 80 C, and the water having a lower boiling point and the trioxane formed in the reaction process enters the fractionation device.According to the principle that the boiling point of paraformaldehyde is lower than water, the triacetal is fractionated back to the reaction unit through a fractionation device.The reaction was carried out as a raw material, and the reaction was completed for 5 hours to obtain glycerol formal, and the product was analyzed by HPLC-MS.At 96.3%, the ratio of the six-membered ring product to the product of the five-membered ring in the product was 70:25. |
With Dowex 50; In toluene; at 100℃;Dean-Stark; Reflux; | A 250 mL three neck flask equipped with a stirrer, an addition funnel, and a Dean-Stark trap was charged with glycerol (9.2 g, 0.1 mol), paraformaldehyde (2.7 g, 0.09 mol), activated ion exchange resin Dowex 50 (10 wt.%), and anhydrous toluene (70 mL). The reaction mixture was refluxed until calculated amount of water was distilled off. The mixture was cooled and filtered. The solvent was removed in low vacuum. Distillation of the residue afforded a mixture of compounds 1a and 1b in the yield of 9.2 g (93%), b.p. 190-195 C (760 Torr). An isomeric ratio was determined by 1H NMR spectroscopy from the integrated intensity ratio of the signals of H(4) methyne protons (deltaH 3.5-4.0) of dioxolane 1a and H(5) methyne proton (deltaH 3.5-4.0) of dioxane 1b. Compound 1a. MS (EI, 70 eV), m/z (Irel (%)): 103 [M - H]+ (not detected), 73 (75), 57 (15), 45 (100), 31 (15). Compound 1b. MS (EI, 70 eV), m/z (Irel (%)): 103 [M - H]+ (not detected), 87 (1), 74 (31), 45 (17), 44 (100), 31 (12). | |
With 1,3,5-Trioxan; at 80℃; for 5.0h; | 920 g of glycerin, 990 g of trioxane and 20 g of the supported solid superacid catalyst prepared in Example 2 were charged into a reaction apparatus, and heated to 80 C to react, and the lower boiling water and trioxane formed during the reaction were fractionated. The device, according to the principle that the boiling point of the paraformaldehyde is lower than water, the triacetal is fractionated back to the reaction device through the fractionation device to continue the reaction as a raw material, and the reaction is finished for 5 hours, thereby obtaining glycerol formal, which is analyzed by HPLC-MS. The yield of the product was 93.5%, and the ratio of the product of the six-membered ring product to the product of the five-membered ring was 77:23. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 2.0h; | Example 14 and Example 15; In 2 ml of tetrahydrofuran were dissolved 224 mg of <n="183"/>the compound represented by the formula (IIa-1) and 125 mg of <strong>[4740-78-7]glycerol formal</strong>, 50 mg of sodium hydride was added under ice-cooling, and the mixture was stirred at room temperature for 2 hours. Thereafter, an aqueous saturated ammonium chloride was added to the reaction mixture, followed by extraction with t-butyl methyl ether. The organic layer was dried with sodium sulfate, and concentrated under reduced pressure. The residue was subjected to medium pressure preparative liquid chromatography to obtain 67 mg of a compound represented by the formula (14) :(hereinafter, referred to as present compound (14)) and 74 mg of a compound represented by the formula (15) :(hereinafter, referred to as present compound (15) . Present compound (14)1H-NMR (CDCl3, TMS) delta (ppm) : 5.07 (IH, s) , 4.93 (IH, s), 4.59 (2H, m) , 4.47 (IH, m) , 4.04 (IH, dd) , 3.79 (IH, dd) , '3.04 (6H, br)Present compound (15)1H-NMR (CDCl3, TMS) delta (ppm): 5.06 (IH, m) , 5.03 (IH, d) , <n="184"/>4.83 (IH, d) , 4.26 (2H, dd) , 4.08 (2H, dd) , 3.04 (6H, br) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride; In tetrahydrofuran; at 0 - 20℃; for 2.0h; | Example 129 and, Example 130; In 2 ml of tetrahydrofuran were dissolved 532 mg of a 'compound represented by the formula (IIa-2) and 230 mg of <strong>[4740-78-7]glycerol formal</strong>, 100 mg of sodium hydride (60% oily) was added under ice-cooling, and the mixture was stirred at <n="242"/>room temperature for 2 hours. Thereafter, an aqueous saturated ammonium chloride solution was added to the reaction mixture, followed by extraction with t-butyl methyl ether. The organic layer was dried with sodium sulfate, and concentrated under reduced pressure. The residue was subjected to medium pressure preparative liquid chromatography to obtain 210 mg of a compound represented by the formula (129) :(hereinafter, referred to as present compound (129)) and 204 mg a compound represented by the formula (130) :(hereinafter, referred to as present compound (130)) .Present compound (129) 1H-NMR (CDCl3, TMS) delta (ppm) : 5.07 (IH, s), 4.93 (IH, s),4.59 (2H, m) , 4.47 (IH, m) , 4.04 (IH, dd) , 3.80 (IH, dd) ,3.72 (4H, t) , 3.57 (4H, s)Present compound (130)'1H-NMR (CDCl3, TMS) delta (ppm): 5.06 (IH, m) , 5.03 (IH, d) , 4.83 (IH, d) , 4.25 (2H, dd) , 4.08 (2H, dd) , 3.72 (4H, t) ,3.56 (4H, s) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; In dichloromethane; at 5 - 20℃; for 2.16667h; | EXAMPLE 2.; 2-GLA <strong>[4740-78-7]glycerol formal</strong> (aka: 5-y-linolenoyloxy)-l,3-dioxan and 5-d,3-dioxanvD- methyl-gamma-linolenate); For the purposes of this exemplification, the synthesis of this ester was carried out by acylation of the commercially available <strong>[4740-78-7]glycerol formal</strong> mixture using gamma-linolenoyl chloride. By this method a mixture of two products is formed and these were separable by column chromatography. The undesired by-product is eluted off the column first; further elution gives the desired acetal-ester. It is a yellow oil at room temperature and appears to have stability properties similar to GLA, stable in air at room temperature for short periods (days) but is best stored long term in a cool place under nitrogen.ExperimentalOxalyl chloride (2.6 ml, 3.78 g, 30 mmol, 1.5 equiv) was added to a solution of gamma- linolenic acid (GLA, 5.56 g, 20 mmol. 1.0 equiv) in dichloromethane (DCM, 40 ml). The resulting solution was stirred under N2 at room temperature overnight and then concentrated in vacuo. The residual oily gamma-linolenoyl chloride was added dropwise EPO <DP n="17"/>over 10 min to a stirred solution of <strong>[4740-78-7]glycerol formal</strong> (2.50 g, 24 mmol, 1.2 equiv) in DCM (40 ml) containing pyridine (10 ml, 9.78 g, 0.12 mol, 6 equiv) at 5 0C. The reaction mixture was stirred at room temperature for 2h, the precipitated pyridine hydrochloride filtered off, and the filtrate washed with water (2 x ). After drying over MgSO4 the solvent was removed in vacuo to give a light tan oil (6.5 g). This material was chromatographed on silica (60 g). Elution with hexane-ether (94:6) gave 5.2 g of an oil consisting of two components (TLC, HPLC). These were separated on a second silica column (6Og). Elution with hexane-ether (98:2 then 95:5) gave 4-(gamma- linolenoyloxymethyl)- 1,3-dioxolane as a yellow oil (1.2 g, 98% by HPLC). deltaH (500 MHz, CDCl3) 0.89 (3H, t, J= 7.0 Hz, CH3), 1.24-1.45 (8H, complex m, 4 x CH2), 1.65 (2H, p, J= 7.5 Hz5 CH2-C-CO), 2.08 (4H1 m, 2 x CH2C=C), 2.35 (2H3 1, J = 7.5 Hz, CH2CO), 2.80 (4H, t, J = 6.0 Hz, 2 x C=CCH2C=C), 3.67 (IH, m, OCITLambdaHB), 3.97 (IH, m, OCHAi2s), 4.14 (2H5 m, OCHAHB), 4.26 (IH, p, J= 3.5 Hz5 CHO)5 4.89 and 5.02 (2H, 2 x s, OCH2O)5 5.36 (6H, m, 3 x CH=CH). deltac (126.8 MHz, CDCl3) 14.09 (CH3), 22.60, 24.51, 25.65, 26.85, 27.23, 29.16, 29.34, 31.53, 33.97, 63.93 (CH2O), 66.72 (CH2O), 73.31 (CHO)5 95.44 (OCO), [127.60, 128.04, 128.32, 128.41, 129.50, 130.41, olefmic C], 173.26 (carbonyl).Further elution gave 5-(gamma-linolenoyloxy)-l,3-dioxan as a yellow oil (1.6 g, 97.8%) by HPLC). deltaH (500 MHz, CDCl3) 0.89 (3H, t, J= 7.0 Hz, CH3), 1.24-1.46 (8H, complex m, 4 x CH2), 1.67 (2H5 p, J = 7.5 Hz, CH2-C-CO)5 2.05 (4H5 m, 2 x CH2C=C), 2.40 (2H, t, J = 7.5 Hz, CH2CO), 2.81 (4H, t, J = 6.0 Hz, 2 x C=CCH2C=C)5 3.91 (2H5 m, OCH2), 3.99 (2H5 m, OCH2), 4.73 (IH5 p, J= 3.5 Hz5 CHO)5 4.80 (IH, d, J = 6.0 Hz, OCHAHBO), 4.93 (IH, d, J = 6.0 Hz, OCHANo.*O), 5.37 (6H5 m, 3 x CH=CH). deltac (126.8 MHz5 CDCl3) 14.08 (CH3), 22.59, 24.53, 25.65, 26.86, 27.22, 29.06, 29.34, 31.52, 34.12, 65.54 (CHO), 68.55 (CH2O), 93.66 (OCO), [127.60, 128.05, 128.32, 128.42, 129.51, 130.42, olefmic C]5 173.12 (carbonyl). Some fractions containing both compounds were obtained during the chromatography and these could be recycled if necessary to give more material. The reaction scheme for this synthesis is shown in the figures below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In pyridine; di-isopropyl ether; glycerol; | PREPARATION H 1,3-Dioxacyclohex-5-yl p-Toluenesulfonate p-Toluenesulfonyl chloride (38.1 g, 0.2 mole) was added to a solution of 20.8 g (0.2 mole) <strong>[4740-78-7]glycerol formal</strong> (a mixture comprised of 67% 1,3-dioxan-5-ol and 33% (1,3-dioxolan-4-yl)methanol) in 200 ml. pyridine cooled to 0 C. under nitrogen. The reaction mixture was stirred at 0 C. for 1/2 hr., then at 25 C. for 20 hr. The mixture was added to 500 ml. 6N aqueous hydrochloric acid solution and the resulting mixture was extracted with four 200 ml. portions of ethyl acetate. The combined ethyl acetate extracts were washed with two 200 ml. portions of lN aqueous hydrochloric acid solution, two 200 ml. portions of water and 200 ml. saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo to an oil. The crude product was dissolved in 500 ml. di-isopropyl ether whereupon the desired 1,3-dioxacyclohex-5-yl tosylate crystallized. Filtration yielded 17.4 g of white crystalline tosylate, m.p. 91-92 C. Another 4.3 g of crystalline tosylate was obtained from the mother liquors (total yield 42%). The NMR spectrum of the title compound as a deuterochloroform solution had peaks at 2.45 (s,3H); 3.54-4.13 (c,4H); 4.26-4.6 (m,1H), 4.75 (s,2H); 7.3 (d,2H); and 7.8 (d, 2H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With pretreated aluminium vanadium phosphate; In water; at 280℃; under 760.051 Torr;Catalytic behavior; Activation energy; | The glycerol transformation was carried out in a continuous-flow fixed-bed reactor under atmospheric pressure, as previouslydescribed [23]. The reactor was made of stainless-steel tubing(7 mm internal diameter and 190 mm long), placed in a tubularelectric furnace. The temperature was monitored by a thermocou-ple located in the catalyst bed. The analysis of the feed and reactionproducts was carried out on-line using a multicolumn gas chro-matograph (GC) equipped with both flame ionization (FID) andthermal conductivity (TCD) detectors in parallel. The compoundswere separated in a capillary column, DB-1 (100% methylpolysilox-ane, 60 m x 0,25 mm x 0,25 m).The catalyst (100 mg) was pretreated at the reaction tempera-ture during 2 h in a N2flow (75 mL/min). A 36 wt% glycerol (99.5%,Sigma-Aldrich) aqueous solution was fed at 0.6 mL/h (0.69 mol/sof glycerol). In general, each catalytic test was conducted at least for3 h at different temperatures (220C, 250C and 280C). The reac-tion products were identified by chromatographic patterns and/or agas chromatograph-mass spectrometer (GC-MS) (VARIAN CP 3800,QUADRUPOLE MS 1200) also equipped with a capillary column DB-1. A blank test showed the absence of homogeneous reactions andthe reactor inactivity in the absence of a catalyst. |
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