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Chemical Structure| 100124-07-0

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Phenoxathiin-4-ylboronic acid

CAS No.: 100124-07-0

4.5 *For Research Use Only !

Cat. No.: A516427 Purity: 95%

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Product Details of [ 100124-07-0 ]

CAS No. :100124-07-0
Formula : C12H9BO3S
M.W : 244.07
SMILES Code : OB(O)C1=C2OC3=CC=CC=C3SC2=CC=C1
MDL No. :MFCD01605731
Boiling Point : No data available
InChI Key :IIENVBUXFRSCLM-UHFFFAOYSA-N
Pubchem ID :2734376

Safety of [ 100124-07-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H319-H315-H335
Precautionary Statements:P261-P352-P280-P305+P351+P338

Calculated chemistry of [ 100124-07-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 66.91
TPSA ?

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

74.99 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.5
Log Po/w (WLOGP)?

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

1.62
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.

1.68
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

0.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.34

Water Solubility

Log S (ESOL):?

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

-3.38
Solubility 0.101 mg/ml ; 0.000412 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.

-3.72
Solubility 0.0465 mg/ml ; 0.00019 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

-3.66
Solubility 0.0539 mg/ml ; 0.000221 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

No
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

Yes
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

Yes
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.

-6.01 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

0.0
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.

0.0 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)

3.4

Application In Synthesis [ 100124-07-0 ]

* 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 [ 100124-07-0 ]

[ 100124-07-0 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 100124-07-0 ]
  • [ 351002-11-4 ]
  • 2-morpholin-4-yl-8-phenoxathiin-4-yl-chromen-4-one [ No CAS ]
  • 2
  • [ 88-04-0 ]
  • [ 100124-07-0 ]
  • 3,5-dimethyl-4-phenoxathiin-4-yl-phenol [ No CAS ]
  • 3
  • [ 100124-07-0 ]
  • [ 119671-47-5 ]
  • [ 587871-28-1 ]
YieldReaction ConditionsOperation in experiment
41% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 90℃; for 24h;Sonication; Example 2 Synthesis of 2-Phenoxathiin-4-yl-6-morpholin-4-yl-pyran-4-one (5) 2-Chloro-6-morpholin-4-yl-pyran-4-one (3)(863 mg, 4 mmol), <strong>[100124-07-0]phenoxathiin-4-boronic acid</strong> (1.07 g, 4.4 mmol), and ground potassium carbonate (1.1 g, 8 mmol) were suspended in dioxane (10 ml) and degassed (sonication for 5 minutes then saturated with N2). Pd(PPh3)4 (231 mg, 0.2 mmol) was then added and the reaction mixture was then heated at 90 C. for 24 hours under a vigorous stirring and a N2 atmosphere. The solvent was removed in vacuo and the residue was then suspended in water (50 ml) and extracted with ethyl acetate (3*50 ml). The organics were combined, washed with saturated brine and dried over sodium sulphate. The solvent was removed in vacuo and the residue was purified by column chromatography (silica; ethyl acetate:ethanol; 9:1) to give the title compound as a white solid (620 mg, 41%). 1H-NMR (300 MHz, DMSO-d6): δ=3.38 (4H, t, J 5 Hz); 3.71 (4H, t, J 5 Hz); 5.49 (1H, d, J 2 Hz); 6.49 (1H, d, J 2 Hz); 7.06 (1H, dd, J 1 and 8 Hz); 7.26 (4H, m); 7.46 (1H, dd, J 1.5 and 8 Hz); 7.55 (1H, dd, J 1.5 and 8 Hz). m/z (LC-MS, ESP): 380 (M++1).
  • 4
  • [ 100124-07-0 ]
  • [ 209808-18-4 ]
  • C34H38N2O4S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; water; toluene; at 90℃; for 24h; N,N-Diethyl-4-(4-phenoxathiinyl-4-piperidinylidenemethyl)- benzamide To a mixture of INTERMEDIATE 5 (0.202 g, 0.448 mmol), 4-PHENOXATHIINYL boronic acid (0.164 g, 0.672 MMOL), toluene (3.6 mL), ethanol (0.84 mL), and 2.0 M NA2CO3 (0.56 mL) in a N2 purged vial was added palladium tetrakistriphenylphosphine (0. 0518 g, 0.045 mmol). The resulting mixture was heated at 90 C for 24 h. The reaction was then concentrated in vacuo and the residue was diluted with water (4 mL) and CH2CI2 (4 mL). The layers were separated, and the aqueous phase was extracted with CH2CI2. The combined organic phases were dried over NA2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography eluting with 5: 1 CH2CI2 : EtOAc. The purified product was dissolved in CH2CI2 (10 mL) and trifluoroacetic acid (1 mL) was added. After 1.5 h, the reaction was concentrated in vacuo. The residue was LYOPHILIZED from CH3CN/H20 to give COMPOUND 3 as its trifluoroacetic acid salt (0.250 g, 95%) as a slightly yellow solid. Purity (HPLC): > 99% ; H NMR (400MHZ, CD30D) 8 1.06 (br t, J = 6.9 Hz, 3H), 1.22 (br t, J = 7.2 Hz, 3H), 2.44-2. 58 (m, 2H), 2.63-2. 73 (m, 1 H), 2.74-2. 83 (m, L H), 3.18-3. 28 (m, 5H), 3.31-3. 40 (m, 1 H), 3.52 (br q, J = 7.4 Hz, 2H), 6.75 (dd, J = 1.3 Hz, 7.9 Hz, IH), 6.98-7. 13 (m, 5H), 7.14-7. 17 (M, 1H), 7. 35 (s, 4H).
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 24h; To a mixture of INTERMEDIATE 5 (0.202 g, 0.448 MMOL), 4-phenoxathiinyl boronic acid (0.164 g, 0.672 MMOL), toluene (3.6 mL), ethanol (0.84 mL), and 2.0 M NA2CO3 (0.56 mL) in a N2 purged vial was added palladium tetrakistriphenylphosphine (0. 0518 g, 0.045 MMOL). The resulting mixture was heated at 90 C for 24 h. The reaction was then CONCENTRATED IN VACUO and the residue was diluted with water (4 mL) and CH2CI2 (4 mL). The layers were separated, and the aqueous phase was extracted with CH2CI2. The combined organic phases were dried over NA2SO4, filtered, and CONCENTRATED IN VACUO. The crude product was purified by silica gel column chromatography eluting with 5: 1 CH2CI2 : EtOAc. The purified product was dissolved in CH2CI2 (10 mL) and trifluoroacetic acid (I mL) was added. After 1. 5 h, the reaction was CONCENTRATED IN VACUO. The residue was LYOPHILIZED from CH3CN/H20 to give COMPOUND 3 as its trifluoroacetic acid salt (0.250 g, 95%) as a slightly yellow solid. Purity (HPLC) : > 99% ; H NMR (400MHZ, CD30D) 8 1.06 (br t, J = 6.9 Hz, 3H), 1.22 (br t, J = 7.2 Hz, 3H), 2.44-2. 58 (m, 2H), 2.63-2. 73 (M, 1H), 2.74-2. 83 (m, 1 H), 3.18-3. 28 (m, 5H), 3. 31-3. 40 (m, 1H), 3.52 (br q, J = 7.4 Hz, 2H), 6.75 (dd, J = 1. 3 Hz, 7.9 Hz, 1H), 6.98-7. 13 (m, 5H), 7.14-7. 17 (m, 1 H), 7. 35 (s, 4H).
  • 5
  • [ 100124-07-0 ]
  • [ 81290-20-2 ]
  • [ 109272-31-3 ]
  • 6
  • [ 100124-07-0 ]
  • [ 24386-93-4 ]
  • 4-amino-5-(phenoxathiin-4-yl)-7-(β-D-ribofuranosyl)-7H-pyrrolo[2,3-d]pyrimidine [ No CAS ]
  • 7
  • [ 610-94-6 ]
  • [ 100124-07-0 ]
  • C20H14O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 8h;Inert atmosphere; 4-phenoxathiinyl boronic acid 18.8g (76.88mmol),methyl-2-bromo-5-chloro-benzoate 18.2g (84.57mmol) and tetrakis triphenylphosphinepalladium0.89g (0.769mmol) were placed in a flask, and under a nitrogen atmosphere, itwas dissolved in tetrahydrofuran 257 ml, and then an aqueous solution 128ml of dissolved potassium carbonate 17g (115.3mmol) was added, and stirred at reflux at 70 Cfor 8 h. After completion of the reaction, it was extracted with ethyl acetate,the extract was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography using n-hexane / ethyl acetate (9: 1 volume ratio) to obtain intermediate M-22 of the desired compound 23.4 g (91% yield).
83% With tetrakis(triphenylphosphine) palladium(0); tetrabutylammomium bromide; potassium carbonate; In water; toluene; at 80℃; for 6h;Inert atmosphere; 2.7g (11mmol) of phenoxi-4-boronic acid, 2.38g (11mmol) of methyl 2-bromobenzoate, 3.06g (22mmol) of potassium carbonate,A mixture of 0.1278 g (0.1 mmol) of tetrakis (triphenylphosphine) palladium and 0.0357 g (0.1 mmol) of tetrabutylammonium bromide was added to a 100 mL three-necked flask, and a mixed solvent of toluene / water of 20 mL / 10 mL was added to the flask ,After replacing the air in the clean flask with nitrogen, the temperature was raised to 80 C under stirring for 6 hours.The reaction solution was washed with water and dried over anhydrous magnesium sulfate, and the organic phase was distilled under reduced pressure to remove toluene.The obtained solid was recrystallized with ethyl acetate to obtain compound 4-1 (compound4-1) (2.91 g, yield 83%).
  • 8
  • [ 27007-53-0 ]
  • [ 100124-07-0 ]
  • C20H13ClO3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; at 70℃; for 8h;Inert atmosphere; 4 -phenoxathiinyl boronic acid 18.8g (76.88mmol),methyl-2-bromo-5-chloro-benzoate 21.1g (84.57mmol) and tetrakis triphenylphosphinepalladium0.89g (0.769mmol) were placed in a flask, and under a nitrogen atmosphere, itwas dissolved in tetrahydrofuran 257 ml, and then an aqueous solution 128ml of dissolvedpotassium carbonate 17g (115.3mmol) was added, and stirred at reflux at 70 C for 8 h. After completion of the reaction, it was extracted with ethyl acetate,the extract was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The product was purified by silica gelcolumn chromatography using n- hexane / ethyl acetate (9: 1 volume ratio) to obtain intermediate M-3 of the desired compound 26.1 g (92% yield).
  • 9
  • [ 262-20-4 ]
  • [ 5419-55-6 ]
  • [ 100124-07-0 ]
YieldReaction ConditionsOperation in experiment
68% Intermediate 1 (30 g, 145 mmol) was added to 300 mL of tetrahydrofuran (THF) and cooled to -78 C. After that, n-butyllithium (n-BuLi) (72 mL, 180 mmol) was slowly added dropwise over 1 hour while stirring, and the reaction was carried out for 1 hour, followed by raising the temperature to room temperature and reacting for 2 hours. After cooling to -78 C. again, triisopropyl borate (33.8 g, 180 mmol) was slowly charged. After further reaction for 2 hours, the temperature was slowly raised to room temperature and reacted for 4 hours.After the reaction, dilute hydrochloric acid (HCl) was added to terminate the reaction, the aqueous layer and the organic layer were separated, and the organic layer was distilled under reduced pressure and extracted with chloroform (1 L) / water (1 L).The solution was dried over magnesium sulfate, and then the organic layer was distilled under reduced pressure. Hexane was used to manufacture Intermediate 4 (25 g, 68%).
  • 10
  • [ 100124-07-0 ]
  • C35H20F9N3O3S [ No CAS ]
  • C43H27N3OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% Intermediate 8 (20.0 g, 27 mmol) and Intermediate 4 (6.7 g, 27 mmol) were placed in 200 mL of tetrahydrofuran (THF) under nitrogen atmosphere, stirred and refluxed.After that, potassium carbonate (K2CO3) (7.5 g, 54.5 mmol) was dissolved in 30 mL of water and charged. After sufficiently stirring, tetraphenylphosphine palladium (0.9 g, 0.8 mmol) was charged. After 6 hours of reaction, the temperature was lowered to room temperature and filtered.After the filtrate was extracted with chloroform and water, the organic layer was dried over magnesium sulfate. After that, the organic layer was distilled under reduced pressure and recrystallized with ethyl acetate. The resulting solid was filtered and dried to produce Compound 1 (9.3 g, 54%).
  • 11
  • [ 100124-07-0 ]
  • C35H20F9N3O3S [ No CAS ]
  • C43H27N3OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% Under a nitrogen atmosphere,Intermediate 8A (20.0 g, 27 mmol) and Intermediate 4 (6.7 g, 27 mmol) manufactured by the same method as the synthesis example of the above Intermediate 8 were added to 200 mL of tetrahydrofuran (THF), and the mixture was stirred and refluxed.After that, potassium carbonate (K2CO3) (7.5 g, 54.5 mmol) was dissolved in 30 mL of water and charged. After sufficiently stirring, tetraphenylphosphine palladium (0.9 g, 0.8 mmol) was charged. After 6 hours of reaction, the temperature was lowered to room temperature and filtered.After the filtrate was extracted with chloroform and water, the organic layer was dried over magnesium sulfate. After that, the organic layer was distilled under reduced pressure and then recrystallized with ethyl acetate. The resulting solid was filtered and dried to produce Compound 4 (12.3 g, 71%).
  • 12
  • [ 100124-07-0 ]
  • C35H20F9N3O3S [ No CAS ]
  • C43H27N3OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% Under a nitrogen atmosphere,Intermediate 8B manufactured by the same method as the synthesis example of the above intermediate 8 was used(20.0 g, 27 mmol) and Intermediate 4 (6.7 g, 27 mmol) were added to 200 mL of tetrahydrofuran, stirred and refluxed.After that, potassium carbonate (K2CO3) (7.5 g, 54.5 mmol) was dissolved in 30 mL of water and charged. After sufficiently stirring, tetraphenylphosphine palladium (0.9 g, 0.8 mmol) was charged. After 6 hours of reaction, the temperature was lowered to room temperature and filtered.After the filtrate was extracted with chloroform and water, the organic layer was dried over magnesium sulfate. After that, the organic layer was distilled under reduced pressure and then recrystallized with ethyl acetate. The resulting solid was filtered and dried to produce compound 5 (7.6 g, 44%).
  • 13
  • [ 109-04-6 ]
  • [ 100124-07-0 ]
  • 2-(phenoxathiin-4-yl)pyridine [ No CAS ]
  • 14
  • [ 100124-07-0 ]
  • C7H6ClFO2S2 [ No CAS ]
  • C13H8ClFOS2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydrogencarbonate; copper(II) sulfate; In methanol; at 10 - 30℃; for 12h;Inert atmosphere; Sealed tube; General procedure: Operation steps: Under the condition of argon protection, weigh 0.9mmol boric acid,0.5mmol reagent, 0.05mmol copper sulfate, 0.75mmol sodium bicarbonate,5 mL of methanol was placed in a 25 mL sealed tube and reacted at room temperature for 12 h. After the reaction is over,10 mL of water was added, extracted with anhydrous ether, dried over anhydrous magnesium sulfate, filtered through celite, and concentrated. The residue was subjected to flash silica gel column chromatography to obtain 135 mg of a colorless oily liquid.The yield was 90%.
  • 15
  • [ 100124-07-0 ]
  • [ 219745-18-3 ]
  • 1-(4-(phenoxathiin-4-yl)phenyl)propane-1,3-diol [ No CAS ]
 

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