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Chemical Structure| 2785-78-6 Chemical Structure| 2785-78-6

Structure of 2785-78-6

Chemical Structure| 2785-78-6

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Product Details of [ 2785-78-6 ]

CAS No. :2785-78-6
Formula : C8H10O2
M.W : 138.16
SMILES Code : OC1=C(C)C=CC(C)=C1O
MDL No. :MFCD24713417
InChI Key :RGUZWBOJHNWZOK-UHFFFAOYSA-N
Pubchem ID :11469114

Safety of [ 2785-78-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 2785-78-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.25
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 40.42
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

40.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.71
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

1.94
Log Po/w (WLOGP)?

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

1.71
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.

1.48
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

1.79
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.73

Water Solubility

Log S (ESOL):?

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

-2.36
Solubility 0.599 mg/ml ; 0.00434 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.41
Solubility 0.533 mg/ml ; 0.00385 mol/l
Class?

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

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

-1.99
Solubility 1.4 mg/ml ; 0.0102 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

Yes
Log Kp (skin permeation)?

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

-5.77 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.

0.55

Medicinal Chemistry

PAINS?

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

1.0 alert
Brenk?

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

1.0 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)

1.0

Application In Synthesis of [ 2785-78-6 ]

* 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 [ 2785-78-6 ]

[ 2785-78-6 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 2785-78-6 ]
  • 2,3-bis-benzoyloxy-1,4-dimethyl-benzene [ No CAS ]
  • 4
  • [ 854037-69-7 ]
  • [ 2785-78-6 ]
  • 5
  • [ 110-91-8 ]
  • [ 2785-78-6 ]
  • [ 72744-93-5 ]
  • 6
  • [ 25163-62-6 ]
  • [ 2785-78-6 ]
YieldReaction ConditionsOperation in experiment
With palladium 10% on activated carbon; hydrogen; In tetrahydrofuran; at 70℃; under 37494.2 Torr; for 48.0h; A mixture of 4 (12.3 g, 40 mmol) and 10% Pd/C (3.7 g) in dry THF (60 mL) was hydrogenated at 70 C under 725 psi of hydrogen gas for 48 h. The crude mixture was filtered through Celite, and the solvent was evaporated to afford dimethyl catechol 5, which was subjected to the next step without purification. Aluminum (III) chloride (21.3 g, 160 mmol) was slowly added to a solution of crude 5 and triethyl orthoformate (13.3 mL, 80 mmol) in dry toluene (150 mL), and the mixture was stirred at 60C for 2 h until TLC indicated complete conversion of the starting material. Hydrochloric acid (3 N, 17 mL) was added, and the reaction mixture was further stirred at rt for 1 h. Ethyl acetate (500 mL) was then added, the reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. The resulting residue was dissolved in ethyl acetate (500 mL), washed with brine (500 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure. Since NMR and MS analyses of the residue showed the formation of 6, the crude material was subjected to the next reaction without purification. Benzyl bromide (23.2 mL, 196.1 mmol) was added dropwise to a solution of crude 6, potassium carbonate (37.8 g, 273.5 mmol) and potassium iodide (3.0 g, 18.1 mmol) in dry acetone (100 mL), and the mixture was refluxed for 13h. The solution was diluted with ethyl acetate (400 mL), washed with brine (3 x300 mL), and dried over sodium sulfate. After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel (3:1 n-hexane - ethyl acetate) to give 444 mg (total yield from 4: 3.2%) of compound 7.
  • 7
  • [ 109451-36-7 ]
  • [ 2785-78-6 ]
  • 9
  • [ 54489-06-4 ]
  • [ 2785-78-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogen;palladium 10% on activated carbon; In ethanol; at 80℃; under 45004.5 Torr; Morpholine (86 g; 0.987M) and formaldehyde (35% strength solution in water, 86 g; IM) in 250 ml of isopropanol are boiled under reflux for 10 minutes and cooled to 0 C. and a solution of 3-methylpyrocatechol (124 g; IM) in 400 ml of isopropanol is added dropwise over the course of 15 minutes. The reaction mixture is boiled under reflux for 15 minutes, cooled and concentrated in vacuo and the residue is recrystallized from isopropanol. [0358] This gives 156.5 g of the compound B2 (purity 99% by LC/MS). [0359] The compound B2 (117.44 g; 0.526M) is dissolved in 2 1 of ethanol, 48 g of 10% palladium on charcoal are added and the mixture is hydrogenated at 80 C. overnight under 60 bar of hydrogen. The hydrogenation mixture is freed from the catalyst by filtration over Kieselguhr, the filtrate is concentrated in vacuo, the residue is dissolved in chloroform and the solution is washed in succession with dilute hydrochloric acid and saturated sodium chloride solution, dried and concentrated in vacuo. [0360] This gives 34.02 g of the compound C2 (purity 85% by LC/MS). [0361] A suspension of the compound C2 (36.061 g, 0.222M) and dried, powdered potassium carbonate (108.2 g; 0.783M) in 250 ml of abs. DMF is heated to 110 C. under argon and dibromoethane (147.1 g; 0.783M) is added dropwise over 2 h. After the end of the addition, heating is continued at 110 C. for 30 minutes, the mixture is cooled and filtered with suction, the filtrate is concentrated in vacuo and the residue is dissolved in chloroform and washed 2× with dilute sodium hydroxide solution and 1× with saturated sodium chloride solution. [0362] This gives 35.7 g of the compound D2 (purity 83% by LC/MS). [0363] N-Bromosuccinimide (22.521 g; 0.1265M) is added at -30 C. to the compound D2 (22.891 g; 0.116M) in solution in 450 ml of anhydrous acetonitrile, cooling is removed and the batch is stirred overnight, filtered and concentrated in vacuo. The crude product is purified twice by column chromatography (silica gel, cyclohexane). [0364] This gives 11.6 g of the compound E2 (purity 88% by GC/MS). [0365] n-Butyllithium (15% strength in hexane, 29.58 ml; 0.048M) is added dropwise at -70 C. to the compound E2 (11.6 g, 0.042M) in 100 ml of anhydrous THF and the mixture is stirred at -70 C. for 1 h, then poured onto dry ice and left to stand overnight. Dilute sodium hydroxide solution is added to the residue, the mixture is washed 2× with ether, and acidified with concentrated hydrochloric acid, and the solid is filtered off with suction and dried. [0366] This gives 6.56 g of the compound III-2 (purity 86% by BPLC, contaminated with 12% of 5,7,8-trimethyl-1,4-benzodioxane-6-carboxylic acid), m.p. 202-3 C.
  • 10
  • [ 88-88-0 ]
  • [ 2785-78-6 ]
  • [ 115185-89-2 ]
  • 11
  • [ 74-97-5 ]
  • [ 2785-78-6 ]
  • [ 74131-59-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In water; N,N-dimethyl-formamide; A. 4,7-Dimethyl-1,3-benzodioxole. To a stirred solution of 2.97 g of 3,6-dimethylcatechol and 3.86 g of potassium carbonate in 60 mL of N,N-dimethylformamide are added 1.69 mL of bromochloromethane. A reflux condenser is attached and the mixture heated in an oil bath to 100 C. for 24 hours. The mixture is allowed to cool to room temperature and then is distributed between 100 mL of water and 200 mL of ether. The aqueous layer is separated and extracted with ether. The combined ether layers are dried over magnesium sulfate and concentrated under reduced pressure to yield a red liquid, which is purified by chromatography on silica gel to afford 2.0 g of 4,7-dimethyl-1,3-benzodioxole as a light yellow liquid.
  • 12
  • [ 2785-78-6 ]
  • [ 41024-91-3 ]
  • [ 87681-99-0 ]
  • 13
  • [ 2785-78-6 ]
  • [ 75863-79-5 ]
  • [ 97431-90-8 ]
  • 14
  • [ 2785-78-6 ]
  • [ 88868-28-4 ]
  • [ 87199-26-6 ]
  • 15
  • [ 2785-78-6 ]
  • [ 63364-61-4 ]
  • 16
  • [ 2785-78-6 ]
  • [ 105999-10-8 ]
  • 17
  • [ 2785-78-6 ]
  • 1,4,6,9-Tetramethyldibenzo<b,e><1,4>dioxin-2,3-chinon [ No CAS ]
  • 18
  • [ 106675-93-8 ]
  • [ 2785-78-6 ]
  • 19
  • [ 2785-78-6 ]
  • [ 830-13-7 ]
  • [ 76836-29-8 ]
  • 20
  • [ 85544-72-5 ]
  • [ 2785-78-6 ]
  • 21
  • [ 2785-78-6 ]
  • [ 106-93-4 ]
  • [ 88631-82-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 110℃; for 2.5h; Morpholine (86 g; 0.987M) and formaldehyde (35% strength solution in water, 86 g; IM) in 250 ml of isopropanol are boiled under reflux for 10 minutes and cooled to 0 C. and a solution of 3-methylpyrocatechol (124 g; IM) in 400 ml of isopropanol is added dropwise over the course of 15 minutes. The reaction mixture is boiled under reflux for 15 minutes, cooled and concentrated in vacuo and the residue is recrystallized from isopropanol. [0358] This gives 156.5 g of the compound B2 (purity 99% by LC/MS). [0359] The compound B2 (117.44 g; 0.526M) is dissolved in 2 1 of ethanol, 48 g of 10% palladium on charcoal are added and the mixture is hydrogenated at 80 C. overnight under 60 bar of hydrogen. The hydrogenation mixture is freed from the catalyst by filtration over Kieselguhr, the filtrate is concentrated in vacuo, the residue is dissolved in chloroform and the solution is washed in succession with dilute hydrochloric acid and saturated sodium chloride solution, dried and concentrated in vacuo. [0360] This gives 34.02 g of the compound C2 (purity 85% by LC/MS). [0361] A suspension of the compound C2 (36.061 g, 0.222M) and dried, powdered potassium carbonate (108.2 g; 0.783M) in 250 ml of abs. DMF is heated to 110 C. under argon and dibromoethane (147.1 g; 0.783M) is added dropwise over 2 h. After the end of the addition, heating is continued at 110 C. for 30 minutes, the mixture is cooled and filtered with suction, the filtrate is concentrated in vacuo and the residue is dissolved in chloroform and washed 2× with dilute sodium hydroxide solution and 1× with saturated sodium chloride solution. [0362] This gives 35.7 g of the compound D2 (purity 83% by LC/MS). [0363] N-Bromosuccinimide (22.521 g; 0.1265M) is added at -30 C. to the compound D2 (22.891 g; 0.116M) in solution in 450 ml of anhydrous acetonitrile, cooling is removed and the batch is stirred overnight, filtered and concentrated in vacuo. The crude product is purified twice by column chromatography (silica gel, cyclohexane). [0364] This gives 11.6 g of the compound E2 (purity 88% by GC/MS). [0365] n-Butyllithium (15% strength in hexane, 29.58 ml; 0.048M) is added dropwise at -70 C. to the compound E2 (11.6 g, 0.042M) in 100 ml of anhydrous THF and the mixture is stirred at -70 C. for 1 h, then poured onto dry ice and left to stand overnight. Dilute sodium hydroxide solution is added to the residue, the mixture is washed 2× with ether, and acidified with concentrated hydrochloric acid, and the solid is filtered off with suction and dried. [0366] This gives 6.56 g of the compound III-2 (purity 86% by BPLC, contaminated with 12% of 5,7,8-trimethyl-1,4-benzodioxane-6-carboxylic acid), m.p. 202-3 C.
  • 22
  • [ 2785-78-6 ]
  • [ 122-51-0 ]
  • [ 97073-42-2 ]
YieldReaction ConditionsOperation in experiment
With aluminum (III) chloride; In toluene; at 60℃; for 2.0h; A mixture of 4 (12.3 g, 40 mmol) and 10% Pd/C (3.7 g) in dry THF (60 mL) was hydrogenated at 70 C under 725 psi of hydrogen gas for 48 h. The crude mixture was filtered through Celite, and the solvent was evaporated to afford dimethyl catechol 5, which was subjected to the next step without purification. Aluminum (III) chloride (21.3 g, 160 mmol) was slowly added to a solution of crude 5 and triethyl orthoformate (13.3 mL, 80 mmol) in dry toluene (150 mL), and the mixture was stirred at 60C for 2 h until TLC indicated complete conversion of the starting material. Hydrochloric acid (3 N, 17 mL) was added, and the reaction mixture was further stirred at rt for 1 h. Ethyl acetate (500 mL) was then added, the reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. The resulting residue was dissolved in ethyl acetate (500 mL), washed with brine (500 mL), dried over sodium sulfate, filtered, and evaporated under reduced pressure. Since NMR and MS analyses of the residue showed the formation of 6, the crude material was subjected to the next reaction without purification. Benzyl bromide (23.2 mL, 196.1 mmol) was added dropwise to a solution of crude 6, potassium carbonate (37.8 g, 273.5 mmol) and potassium iodide (3.0 g, 18.1 mmol) in dry acetone (100 mL), and the mixture was refluxed for 13h. The solution was diluted with ethyl acetate (400 mL), washed with brine (3 x300 mL), and dried over sodium sulfate. After removal of the solvent under reduced pressure, the residue was purified by column chromatography on silica gel (3:1 n-hexane - ethyl acetate) to give 444 mg (total yield from 4: 3.2%) of compound 7.
  • 24
  • [ 2785-78-6 ]
  • [ 77-78-1 ]
  • [ 72912-16-4 ]
  • 25
  • [ 2785-78-6 ]
  • [ 920-37-6 ]
  • 5,8-Dimethyl-2,3-dihydro-benzo[1,4]dioxine-2-carbonitrile [ No CAS ]
  • 26
  • [ 7218-22-6 ]
  • [ 2785-78-6 ]
  • 27
  • [ 3921-14-0 ]
  • [ 2785-78-6 ]
  • 28
  • [ 2785-78-6 ]
  • [ 109-89-7 ]
  • [ 72744-95-7 ]
  • 32
  • [ 2785-78-6 ]
  • [ 64248-62-0 ]
  • 2-cyano-6,9-dimethyldibenzo[1,4]dioxine [ No CAS ]
  • 33
  • [ 2785-78-6 ]
  • [ 21524-39-0 ]
  • 1-cyano-6,9-dimethyldibenzo[1,4]dioxine [ No CAS ]
  • 34
  • [ 2785-78-6 ]
  • [ 534-07-6 ]
  • 6,9-dimethyl-2H-1,5-benzodioxepin-3(4H)-one [ No CAS ]
  • 35
  • [ 2785-78-6 ]
  • 5,8-Dimethyl-2,3-dihydro-benzo[1,4]dioxine-2-carboximidic acid methyl ester [ No CAS ]
 

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