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Chemical Structure| 6947-94-0 Chemical Structure| 6947-94-0

Structure of 6947-94-0

Chemical Structure| 6947-94-0

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Product Details of [ 6947-94-0 ]

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

Safety of [ 6947-94-0 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 6947-94-0 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

50.44 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.23
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.91
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.29
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.02
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.09
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.91

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.54
Solubility 3.63 mg/ml ; 0.0288 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.55
Solubility 3.52 mg/ml ; 0.0279 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-1.33
Solubility 5.9 mg/ml ; 0.0468 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.42 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.56

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.25

Application In Synthesis of [ 6947-94-0 ]

* 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.

  • Downstream synthetic route of [ 6947-94-0 ]

[ 6947-94-0 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 6947-94-0 ]
  • [ 5555-00-0 ]
YieldReaction ConditionsOperation 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.
  • 2
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  • [ 97-97-2 ]
  • [ 141-97-9 ]
  • [ 5555-00-0 ]
YieldReaction ConditionsOperation 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.
  • 3
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  • [ 79-37-8 ]
  • [ 5555-00-0 ]
  • 4
  • [ 6947-94-0 ]
  • [ 3416-93-1 ]
  • [ 5555-00-0 ]
 

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