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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
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Structure of 6947-94-0
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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
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CAS No. : | 6947-94-0 |
Formula : | C6H6O3 |
M.W : | 126.11 |
SMILES Code : | O=C(C1=C(C)OC=C1)O |
MDL No. : | MFCD00092314 |
InChI Key : | CFGQZVOVFIZRMN-UHFFFAOYSA-N |
Pubchem ID : | 244756 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅲ |
Num. heavy atoms | 9 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.17 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 30.63 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.44 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.23 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.91 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.02 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.09 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.91 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.54 |
Solubility | 3.63 mg/ml ; 0.0288 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.55 |
Solubility | 3.52 mg/ml ; 0.0279 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.33 |
Solubility | 5.9 mg/ml ; 0.0468 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 |
-6.42 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 |
0.56 |
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) |
2.25 |
* 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 oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 0.5h; | A suspension of 2-methylfuran-3-carboxylic acid [e.g. available from Lancaster Synthesis Ltd] (31.5 mg) in dichloromethane (0.5 ml) was treated with oxalyl chloride (0.022 ml) and DMF (one drop) at room temperature under nitrogen for 0.5 h. The solution was then added dropwise to a stirred solution of Intermediate 16 (69 mg) and DIPEA (0.044 ml) in acetonitrile (1.25 ml) and the mixture stirred for 90 h at room temperature. It was then diluted with dichloromethane (7 ml), washed with dilute aqueous sodium chloride (2×7 ml) and the organic extract applied to an SPE cartridge (Flash NH2). Elution with methanol gave Example 195 as a beige solid (85 mg). LCMS showed MH+=412, TRET=2.31 min. | |
With oxalyl dichloride;N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 0.5h; | Example 195 N-[1 ,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1 H- pyrazolo[3,4-b]pyridin-5-yl]methyl}-2-methyl-3-furancarboxamideA suspension of 2-methyfuran-3-carboxylic acid [e.g. available from Lancaster Synthesis Ltd] (31.5mg) in dichloromethane (0.5ml) was treated with oxalyl chloride (0.022ml) and DMF (one drop) at room temperature under nitrogen for 0.5h. The solution was then added dropwise to a stirred solution of Intermediate 16 (69mg) and DIPEA (0.044ml) in acetonitrile (1.25ml) and the mixture stirred for 9Oh at room temperature. It was then diluted with dichloromethane (7ml), washed with dilute aqueous sodium chloride (2 x 7ml) and the organic extract applied to an SPE cartridge (Flash NH2). Elution with EPO <DP n="189"/>methanol gave Example 195 as a beige solid (85mg). LCMS showed MH+ = 412, TRET : 2.31min. | |
With thionyl chloride; N,N-dimethyl-formamide; In dichloromethane; at 70℃; for 3h; | After dissolving 2-methylfuran-3-carboxylic acid (20 mmol) indichloromethane (20 mL) at room temperature, N,N-dimethylformamide(5-6 drops) and thionyl chloride (15 mL) were added in this order and theresulting mixture was stirred at 70 C for 3 hours. The remaining solventsdichloromethane and thionyl chloride were removed by distillation under reducedpressure to yield the corresponding 3-furoyl chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; hydrogenchloride; sodium hydroxide; In thionyl chloride; ethanol; water; | Step 4 Preparation of 2-methyl-3-furoyl chloride A first reaction mixture of chloroacetaldehyde dimethylacetal (300 g), water (400 mL) and 36% hydrochloric acid (40 mL) was stirred and brought to reflux. When the first reaction mixture became homogenous, it was cooled and added to a stirred solution of ethyl acetoacetate (260 g) and pyridine (500 mL) and left stirring at ambient temperature for 72 hours, to produce a second reaction mixture. The organic layer was then separated from the second reaction mixture and the aqueous layer was diluted with water and then extracted with methylene chloride. The combined organics were washed with 2N hydrochloric acid, followed by removal of the solvent. The residue was treated with a solution of sodium hydroxide (80 g) in water (700 mL) and ethanol (100 mL), to produce a third reaction mixture. After refluxing for 1 hour the third reaction mixture was poured into ice/water and acidified with hydrochloric acid. A cream colored precipitate formed. This precipitate was collected on a filter, washed with water and dried to give 2-methyl-3-furancarboxylic acid, 180 g. 100 g of the 2-methyl-3-furancarboxylic acid was added in portions to thionyl chloride (500 mL) and refluxed for 3 hours. Excess thionyl chloride was then distilled off to produce a residue. The residue was distilled using a water pump, to give 2-methyl-3-furanylcarboxylic chloride, bp. 62 C., 100 g. | |
With pyridine; hydrogenchloride; sodium hydroxide; In thionyl chloride; ethanol; water; | Step 4 Preparation of 2-methyl-3-furoyl chloride A first reaction mixture of chloroacetaldehyde dimethylacetal (300g), water (400 mL) and 36% hydrochloric acid (40 mL) was stirred and brought to reflux. When the first reaction mixture became homogenous, it was cooled and added to a stirred solution of ethyl acetoacetate (260g) and pyridine (500 mL) and left stirring at ambient temperature for 72 hours, to produce a second reaction mixture. The organic layer was then separated from the second reaction mixture and the aqueous layer was diluted with water and then extracted with methylene chloride. The combined organics were washed with 2N hydrochloric acid, followed by removal of the solvent. The residue was treated with a solution of sodium hydroxide (80g) in water (700 mL) and ethanol (100 mL), to produce a third reaction mixture. After refluxing for 1 hour the third reaction mixture was poured into ice/water and acidified with hydrochloric acid. A cream colored precipitate formed. This precipitate was collected on a filter, washed with water and dried to give 2-methyl-3-furancarboxylic acid, 180g. 100g of the 2-methyl-3-furancarboxylic acid was added in portions to thionyl chloride (500 mL) and refluxed for 3 hours. Excess thionyl chloride was then distilled off to produce a residue. The residue was distilled using a water pump, to give 2-methyl-3-furanylcarboxylic chloride, bp. 62C, 100g. |
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