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Chemical Structure| 1255308-97-4 Chemical Structure| 1255308-97-4

Structure of 1255308-97-4

Chemical Structure| 1255308-97-4

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Product Details of [ 1255308-97-4 ]

CAS No. :1255308-97-4
Formula : C18H11NS
M.W : 273.35
SMILES Code : C1(NC2=C3C=CC=C2)=C3C4=C(C5=CC=CC=C5S4)C=C1
MDL No. :MFCD22571687
InChI Key :NPHLAWPEXYBGTP-UHFFFAOYSA-N
Pubchem ID :66585208

Safety of [ 1255308-97-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Computational Chemistry of [ 1255308-97-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 20
Num. arom. heavy atoms 20
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 88.69
TPSA ?

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

44.03 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.58
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

5.74
Log Po/w (WLOGP)?

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

5.69
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.

4.56
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

6.24
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.96

Water Solubility

Log S (ESOL):?

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

-5.89
Solubility 0.000351 mg/ml ; 0.00000129 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-6.43
Solubility 0.000101 mg/ml ; 0.00000037 mol/l
Class?

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

Poorly 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

-7.58
Solubility 0.00000721 mg/ml ; 0.0000000264 mol/l
Class?

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

Poorly 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

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.

-3.89 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

1.0
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.

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)

2.24

Application In Synthesis of [ 1255308-97-4 ]

* 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.

  • Upstream synthesis route of [ 1255308-97-4 ]
  • Downstream synthetic route of [ 1255308-97-4 ]

[ 1255308-97-4 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 530403-00-0 ]
  • [ 1255308-97-4 ]
YieldReaction ConditionsOperation in experiment
90% for 10 h; Reflux General procedure: 4-(2-Nitrophenyl)dibenzo[b,d]furan (10.00 g, 34.57 mmol) wasdissolved in triethylphosphite (100 mL) and refluxed for 10 h. Thereaction mixture was cooled to room temperature and extractedwith ethyl acetate and distilled water. The organic layer was treatedwith anhydrous magnesium sulfate, and the solvent was removedby rotary evaporation. Impurities were removed by column chromatographyon silica gel using dichloromethane/n-hexane toobtain a yellowish powder. The results are as follows:
78.19% at 150℃; for 7 h; Compound 2-1 (10g, 32.74mmol) was mixed with triethylphosphite 100mL, and stirred at 150°C for 7 hours. The mixture was cooled to room temperature and distilled under reduced pressure. Subsequently, recrystallization was conducted using EA, yielding Compound 2-2 (7g, 25.60mmol, 78.19percent).
78.19% at 150℃; for 7 h; Compound 12-1 10g (32.74mmol) was mixed with triethylphosphite 100ml, and then the mixture was stirred at 150 for 7 hours. The resultant material was cooled to room temperature, distilled under reduced pressure, and recrystallized with EA, thereby obtaining Compound 12-2 7g (25.60mmol, 78.19percent).
77.6% With triphenylphosphine In 1,2-dichloro-benzene for 24 h; Inert atmosphere; Heating 500mL of the round bottom flask in a nitrogen atmosphere in M-22 (14.0 g, 45.8 mmol), triphenylphosphine (36 g, 137.5 mmol) dissolved in dichlorobenzene and then to 160 ° C at the 24-hour stirring was dongan.After the reaction the reaction was cooled to room temperature, the dichlorobenzene was removed under reduced pressure. The reaction of methylene chloride / hexane (1: 1) and purified over a silica column with a mixed solvent Kell intermediate M-23 9.7 g (Yield: 77.6percent) was obtained.
76% at 180℃; for 5 h; Inert atmosphere Intermediate I-36 (140 g, 458 mmol) was dissolved in 0.7 L of triethylphosphite in a nitrogen atmosphere,And the mixture was refluxed by heating at 180 DEG C for 5 hours. After completion of the reaction, water is added to the reaction solution After precipitation, it was filtered. The residue thus obtained was purified by flash column chromatographyTo obtain Intermediate I-37 (95.1 g, 76percent).
71.13% With triethyl phosphite In 1,2-dichloro-benzene at 150℃; for 5 h; After mixing compound 3-1 (11 g, 36.02 mmol), P(OEt)3 (100 mL) and 1,2-dichlorobenzene (100 mL), the reaction mixture was stirred at 150°C under reflux. After 5 hours, the reaction mixture was cooled to room temperature, was distillated under reduced pressure, and was filtered through column to obtain compound 3-2 (7 g, 25.60 mmol, 71.13 percent).
70% at 90℃; for 12 h; After mixing compound 2-1 (88 g, 0.29 mol), P(OEt)3 (960 mL, 0.4 M) and triethylphosphite (960 mL), the reaction mixture was stirred for 12 hours at 90°C. After terminating the reaction, the reaction mixture was distilled to remove triethylphosphite, and was filtered through column to obtain compound 2-2 (40 g, 70 percent)
70% at 150℃; for 6 h; After adding compound C-2-1 (88 g, 0.29 mol) to P(OEt)3 (960 mL, 0.4 M), the mixture was stirred for 6 hours at 150°C. After completing the reaction, P(OEt)3 was removed by distillation, and then the remaining product was separated with a column to obtain, white solid, compound C-2-2 (40 g, 70 percent).
61% With triphenylphosphine In 1,2-dichloro-benzene for 24 h; Reflux Dissolve the intermediate C and triphenylphosphine obtained in step 3) in o-dichlorobenzene, was refluxed for 24 hours. After the reaction was completed after using a reduced pressure distillation to remove the solvent, and the concentrated product was separated by column chromatography to obtain the desired intermediate D (yield: 61percent).
61% With triphenylphosphine In 1,2-dichloro-benzene for 24 h; Reflux The intermediate B obtained from the previous step, and triphenylphosphine were dissolved in o-DCB(o-dichlorobenzene), followed by reflux for 24 hours. After the completion of the reaction, vacuum distillation was carried out for removal of a solvent. Then, the concentrated product was purified by column chromatography to give a required intermediate C (yield: 61percent).
60% With triphenylphosphine In 1,2-dichloro-benzene at 180℃; Sub 1-3 (1) (30.5g, 100 mmol), PPh3 (65.5g, 250mmol), after loading the 1,2-dichlorobenzene (500ml) and the reaction proceeds at 180 . After completion of reaction, drying after the removal of 1,2-dichlorobenzene and the organic layer was extracted with water and CH2Cl2 over MgSO4, silicagel column and re-crystallization and the resulting organic material and then concentrated to give 16.4g of Sub 1 (1). (Yield: 60percent)
56% With triethyl phosphite In 1,2-dichloro-benzene for 13 h; Reflux Compound H-2-2 (74.8 g, 245.0 mmol), triethylphosphite [P(OEt)3] (500.0 mL) and 1,2-dichlorobenzene (1,2-DCB) (200.0 mL) were reflux stirred in a 1L RBF. After 13 hours, the solvent was distilled, and the solid was dissolved in CHCl3and was separated through column chromatography on silica gel to obtain compound H-2-3 (38.0 g, 56 percent)
45% With triphenylphosphine In 1,2-dichloro-benzene at 185℃; for 20 h; Intermediate D 13.7g (44.9mmol), in addition triphenylphosphine 29.4g the (112mmol) in o-dichlorobenzene 200ml, and the mixture was stirred at 185° C 20 hours. The solvent was distilled off under reduced pressure, a solid precipitated by addition of methanol was collected by filtration, by heating suspension washing by adding toluene to yield intermediate E 5.5g (45percent yield)
6 g for 12 h; Reflux Compound 31-1 (8 g), triphenylphosphine (20.6 g) and 1,3-dichlorobenzene (56 ml) were placed in a 250 ml three-necked round bottom flask, and the mixture was refluxed and stirred for 12 hours. The solvent was removed by concentration under reduced pressure. Column separation using a dichloromethane and hexane mixed solvent was carried out on the substance produced by concentration to obtain 6 g of the title compound.
6 g for 12 h; Reflux A 250 mL three-necked round bottom flask was charged with 8 g of compound 31-1, Triphenylphosphine (20.6 g) and 1,3-dichlorobenzene (56 mL) were added and the mixture was refluxed and stirred for 12 hours. The solvent was removed by concentration under reduced pressure. The material formed by concentration was dissolved in dichloromethane, 6 g of the title compound was obtained by column separation using a hexane mixed solvent.

References: [1] Chemical Communications, 2015, vol. 51, # 38, p. 8105 - 8107.
[2] Organic Electronics: physics, materials, applications, 2017, vol. 42, p. 66 - 74.
[3] Patent: WO2012/39561, 2012, A1, . Location in patent: Page/Page column 22.
[4] Patent: EP2857395, 2015, A1, . Location in patent: Paragraph 0093.
[5] Patent: KR101486561, 2015, B1, . Location in patent: Paragraph 0505-0508.
[6] Patent: KR2017/124412, 2017, A, . Location in patent: Paragraph 0372-0374.
[7] Patent: WO2013/12296, 2013, A1, . Location in patent: Paragraph 118; 121; 122.
[8] Patent: WO2013/12297, 2013, A1, . Location in patent: Paragraph 102; 105; 106.
[9] Patent: WO2013/122402, 2013, A1, . Location in patent: Paragraph 171; 174; 175.
[10] Patent: KR101497123, 2015, B1, . Location in patent: Paragraph 0097; 0098; 0099; 0100.
[11] Patent: US10020452, 2018, B2, . Location in patent: Page/Page column 42-44.
[12] Patent: KR2016/10915, 2016, A, . Location in patent: Paragraph 0119; 0123; 0124.
[13] Patent: WO2014/185694, 2014, A1, . Location in patent: Paragraph 141; 144; 145.
[14] Patent: JP2015/78169, 2015, A, . Location in patent: Paragraph 0058.
[15] Patent: KR2017/126059, 2017, A, . Location in patent: Paragraph 0205; 0206; 0210; 0211.
[16] Patent: KR2018/131662, 2018, A, . Location in patent: Paragraph 0231-0233; 0236-0237.
  • 2
  • [ 108847-20-7 ]
  • [ 1255308-97-4 ]
References: [1] Patent: WO2013/12297, 2013, A1, .
[2] Patent: WO2013/12296, 2013, A1, .
[3] Patent: WO2013/122402, 2013, A1, .
[4] Patent: EP2857395, 2015, A1, .
[5] Chemical Communications, 2015, vol. 51, # 38, p. 8105 - 8107.
[6] Patent: KR2016/10915, 2016, A, .
[7] Patent: KR101486561, 2015, B1, .
[8] Patent: JP2015/78169, 2015, A, .
[9] Patent: KR101497123, 2015, B1, .
[10] Organic Electronics: physics, materials, applications, 2017, vol. 42, p. 66 - 74.
[11] Patent: KR2017/124412, 2017, A, .
[12] Patent: US10020452, 2018, B2, .
  • 3
  • [ 577-19-5 ]
  • [ 1255308-97-4 ]
References: [1] Patent: WO2013/12297, 2013, A1, .
[2] Patent: EP2857395, 2015, A1, .
[3] Chemical Communications, 2015, vol. 51, # 38, p. 8105 - 8107.
[4] Patent: KR2016/10915, 2016, A, .
[5] Patent: KR101486561, 2015, B1, .
[6] Patent: JP2015/78169, 2015, A, .
[7] Organic Electronics: physics, materials, applications, 2017, vol. 42, p. 66 - 74.
[8] Patent: KR2017/124412, 2017, A, .
  • 4
  • [ 108847-20-7 ]
  • [ 577-19-5 ]
  • [ 1255308-97-4 ]
References: [1] Patent: WO2012/39561, 2012, A1, .
[2] Patent: WO2014/185694, 2014, A1, .
[3] Patent: KR2017/126059, 2017, A, .
[4] Patent: KR2018/131662, 2018, A, .
  • 5
  • [ 132-65-0 ]
  • [ 1255308-97-4 ]
References: [1] Patent: KR101497123, 2015, B1, .
[2] Patent: US10020452, 2018, B2, .
  • 6
  • [ 97511-05-2 ]
  • [ 1255308-97-4 ]
References: [1] Patent: KR101497123, 2015, B1, .
 

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