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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
Inaccessible (Haz class 6.1), International | USD 150+ |
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Accessible (Haz class 3, 4, 5 or 8), International | USD 200+ |
Structure of 78-09-1
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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.
4.5
*For Research Use Only !
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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 78-09-1 |
Formula : | C9H20O4 |
M.W : | 192.25 |
SMILES Code : | CCOC(OCC)(OCC)OCC |
MDL No. : | MFCD00009221 |
InChI Key : | CWLNAJYDRSIKJS-UHFFFAOYSA-N |
Pubchem ID : | 66213 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225 |
Precautionary Statements: | P210-P233-P240-P241-P242-P243-P280-P303+P361+P353-P370+P378-P403+P235-P501 |
Class: | 3 |
UN#: | 3272 |
Packing Group: | Ⅲ |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 8 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.92 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
3.09 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.28 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.74 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.1 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.69 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.31 |
Solubility | 9.41 mg/ml ; 0.0489 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.65 |
Solubility | 4.26 mg/ml ; 0.0221 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.06 |
Solubility | 1.67 mg/ml ; 0.00867 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) |
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 |
-6.56 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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.69 |
* 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 |
---|---|---|
86% | With acetic acid; at 80℃; for 1h; | To a solution of compound 8 in tetraethyl orthocarbonate (5 mL), acetic acid (0.37 g) was added, and the mixture was stirred at 80 °C for 1 h, the reaction mixture was concentrated, and the residue was dissolved in ethyl acetate. Washed with water, evaporated to dryness, The crystal was recrystallized from ethyl acetate-hexane.Obtained 2.01g of colorless crystal,Yield 86percent, compound 5. |
84.8% | With acetic acid; at 78 - 82℃; for 1 - 2h;Heating / reflux; Industry scale; | The concentrate of methyl 3-amino-2-N-[(2'-cyanobiphenyl-4-yl)methyl]aminobenzoate [MBA] obtained in Reference Example5, tetraethyl orthocarbonate [TEC] obtained in Reference Example 6 (397 kg) and acetic acid (62 kg) were mixed, and the mixture was heated (78 to 82°C) under reflux for about 1 to 2 hrs.. The reaction solution was cooled, and methanol (1680 L), a 24percent aqueous sodium hydroxide solution (65 L) and water (2030 L) were added.. The mixture was stirred at 60 to 30°C for 2 hours, and the PH was adjusted to 5 to 7.. After cooled to 5°C or lower, the precipitated crystals were separated, and washed with cold water (2500 L) and cold ethyl acetate (500 L) to give first crystals.. The mother liquor and the washing were concentrated under reduced pressure, followed by cooling to 5°C or lower, and the precipitated crystals were separated, and washed with cold ethyl acetate (20 L) to give second crystals.. The first and second crystals were combined, and dissolved in ethyl acetate (4890 L) under reflux.. A seed crystal was added at about 70°C, and cooled to 5 °C. The crystals were separated, and washed with cold ethyl acetate (200 L), followed by drying to give methyl 1-[(2'-cyanobiphenyl-4-yl)methyl]-2-ethoxybenzimidazole-7-carboxylate [BEC](361 kg, 84.8percent). mp. 168.5-169.5°C 1H-NMR(200MHz, CDCl3) delta: 1.42(3H,t), 3.71(3H,s), 4.63(2H,q), 5.59(2H,s), 7.09(2H,d), 7.20(1H,t), 7.45-7.59(5H,m), 7.69-7.80(2H,m), 7.92(1H,dd) IR(KBr) cm-1: 2225, 1725, 1550, 1480, 1430, 1280, 1250, 1040, 760, 750 |
With acetic acid; In toluene; at 20℃;Reflux; | Example 1; To the solution of Methyl-3-amino-2-[[2'-cyanobiphenyl-4-yl]methyl]amino] benzoate (100 gm) in toluene (500 ml), tetraethyl ortho carbonate (125 gm) and acetic acid (20 gm) were added at room temperature and refluxed for 6 hours.Distilled off toluene under vacuum below 600C, added methanol (300 ml) at 550C, stirred for 20 minutes, cooled to room temperature, filtered and then washed with methanol (90 ml). Dried for 6 hours to yield Methyl-1-[(2-cyano biphenyl-4- yl)methyl]-2-ethoxy benzimidazole-7-carboxylate (90 gm, HPLC purity: 98.9percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.1% | In acetic acid; at 25 - 35℃; for 2 - 3h; | Methyl 2-amino-3-nitrobenzoate (150.0 grams, 0.765 moles) was placed inan autoclave vessel and 1000 mlof ethyl acetate and 75 grams of Raney nickelwere added to the vessel and stirred under a 2-3 kg/cm2 hydrogen pressure for12-15 hours. The catalyst was removed by filtration, and the ethyl acetate wasevaporated under reduced pressure. Acetic acid (170 ml) was added to theresidue, and 180 grams of tetraethylorthocarbonate was slowly added at 25-35°C.The reaction mass was stirred for 2-3 hours, and water (750 ml) was added afterthe reaction mass was cooled to 10°C. The solid was filtered, washed with 150 mlof water, and dried at 50-60°C to get 140 grams (83.1 percent) of methyl 2-ethoxybenzimidazole-7-carboxylate.; 150 grams of 2-Amino-3-nitro-benzoic acid methylester, Raney nickel (75grams), ethyl acetate (1 litre) were charged in an autoclave vessel. 3.0kg/cm2 ofdry hydrogen gas was passed into the reaction suspension for about 20-25 hoursunder agitation. Reaction mass was filtered on celite, followed by washing thecelite with 150 ml of ethyl acetate. Solvent was removed completely from thefiltrate at about 45-50°C by distillation. 171 ml of acetic acid was charged andtetraethylorthocarbonate (180 grams) was added over about 30-45 minutes.Reaction mass was maintained for about 1-3 hours and was cooled to about 0-5°C. 750 ml of water was added over about 15-30 minutes and the separatedsolid was filtered and washed with 150 ml water, followed by 150 ml of ethylacetate. Solid obtained was dried at about 55-65°C for about 10-12 hours to yield140 grams of 2-Ethoxy-3H-benzoimidazole-4-carboxylic acid methylestercompound of Formula (IV). |
With acetic acid; at 25 - 30℃; | (1) Add 120 g of AM5 and 300 ml of glacial acetic acid to the reaction flask.The original tetraethyl carbonate 185g.(2) The reaction is warmed up to 25 to 30°C for 2 to 3 hours. The reaction conditions of the raw materials are observed by spotting until the basic reaction of the raw materials is complete.(3) After the reaction, the water is slowly cooled to 5-10 DEG C and stirred for 2 hours. The mixture is suction filtered, and the solid is washed with water twice and dried to obtain methyl 2-ethoxybenzimidazole-7-carboxylate as a product. |