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Chemical Structure| 247109-15-5 Chemical Structure| 247109-15-5

Structure of 247109-15-5

Chemical Structure| 247109-15-5

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Product Details of [ 247109-15-5 ]

CAS No. :247109-15-5
Formula : C9H9N3OS
M.W : 207.25
SMILES Code : NC1=NN=C(C2=CC=CC(OC)=C2)S1
English Name :5-(3-Methoxyphenyl)-1,3,4-thiadiazol-2-amine
MDL No. :MFCD00628650
InChI Key :ANOZGAXEWJZHBU-UHFFFAOYSA-N
Pubchem ID :819785

Safety of [ 247109-15-5 ]

Computational Chemistry of [ 247109-15-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 11
Fraction Csp3 0.11
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 56.24
TPSA ?

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

89.27 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

1.65
Log Po/w (WLOGP)?

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

1.8
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.

0.94
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

2.41
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.

-2.61
Solubility 0.504 mg/ml ; 0.00243 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.

-3.14
Solubility 0.151 mg/ml ; 0.000728 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

-3.21
Solubility 0.127 mg/ml ; 0.000611 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

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

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

No
Log Kp (skin permeation)?

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

-6.39 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

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)

2.49

Application In Synthesis of [ 247109-15-5 ]

* 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 [ 247109-15-5 ]

[ 247109-15-5 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 1334180-01-6 ]
  • [ 247109-15-5 ]
YieldReaction ConditionsOperation in experiment
With iron(III) chloride In ethanol for 2h; Heating;
  • 2
  • [ 247109-15-5 ]
  • [ 113111-43-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; copper; acetic acid; sodium nitrite at 15 - 20℃; for 4h;
  • 3
  • [ 247109-15-5 ]
  • [ 112764-40-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: conc. HCl, aq. NaNO2, copper, glacial acetic acid / 4 h / 15 - 20 °C 2: 60 percent / 1.) hydrazine hydrate, 2.) HCl / ethanol / 4 h / Heating
  • 4
  • [ 79-19-6 ]
  • [ 586-38-9 ]
  • [ 247109-15-5 ]
YieldReaction ConditionsOperation in experiment
84% Stage #1: thiosemicarbazide; 3-Methoxybenzoic acid With trichlorophosphate at 75℃; for 1h; Stage #2: With water at 20℃; for 4h; Reflux;
56.6% With trichlorophosphate at 20 - 75℃; for 4.5h; 4.2.1. Synthesis of 2-amino-5-aryl-1, 3, 4-thiadiazole derivatives General procedure: The substituted benzoic acid (0.02 mol) and the thiosemicar-bazide (0.02 mol) were mixed and placed in a 100 mL three-necked flask, and then POCl 3 (7 mL) was added dropwise to the3cold mixture with stirring. It was first heated to reflux (75°C,0.5 h) and then cooled to room temperature. 25 mL of water wasadded under cold water bath conditions. Finally, heating to reflu(4 h). TLC (Thin Layer Chromatography) monitored the progress ofthe reaction. After the reaction was completed, stop heating andallow it to cool naturally. 40% NaOH was slowly added to adjustthe pH to 8, filtered to obtain the solid powder, recrystallized fromethanol, and dried to obtain the product.
With trichlorophosphate at 0℃; for 4.5h; Reflux;
With trichlorophosphate
Stage #1: 3-Methoxybenzoic acid With trichlorophosphate at 20℃; for 0.333333h; Stage #2: thiosemicarbazide for 1h; Reflux; 4.1.2.1. Procedure for the synthesis of 2a-o General procedure: A mixture ofcorresponding acid, 1 (2.00 mmol), and POCl3 (0.80 ml) wasstirred for 20 min at room temperature. Then, thiosemicarbazide(2.0 mmol, 0.182 g) was added, and theresulting suspension was refluxed for 1 h. After cooling theflask in an ice bath, 2.4 ml of distilled water was addedcarefully, and refluxwas continued for 1 h. The mixturewasthen cooled to the room temperature, saturated aqueoussolution of NaOH was added until pH 8.5 was reached, andthe suspensionwas stirred for 1 h at the room temperature.The formed precipitate of the corresponding 2-amino-1,3,4-thiadiazole derivative (2aeo) was then filtrated, driedover CaCl2, and recrystallized from hot 50% aqueous EtOH.
With trichlorophosphate at 80℃; for 2.5h; 3.2.1. Preparation of compounds A1-A24 General procedure: A mixture of different forms of substituted benzoic acid (1.0 mmol), thiosemicarbazide (91.1 mg, 1.0 mmol), and POCl3 (0.6 mL) was warmed (150 min at 80 C), cooled toroom temperature, and then 2mL of water was then added to this solution. Solutionwas then refluxed for 240 min, cooled, and adjusted to a pH of 8 via adding NaOH(40%) in a dropwise manner with constant stiring. Resultant precipitate/residue wasthen filtered/passed through column chromatography for generating purified A1-A24with yields from 74-88%.
With trichlorophosphate at 80℃; for 2.5h; 3.2.1. Preparation of compounds A1-A24 General procedure: A mixture of different forms of substituted benzoic acid (1.0 mmol), thiosemicarbazide (91.1 mg, 1.0 mmol), and POCl3 (0.6 mL) was warmed (150 min at 80 C), cooled toroom temperature, and then 2mL of water was then added to this solution. Solutionwas then refluxed for 240 min, cooled, and adjusted to a pH of 8 via adding NaOH(40%) in a dropwise manner with constant stiring. Resultant precipitate/residue wasthen filtered/passed through column chromatography for generating purified A1-A24with yields from 74-88%.
With trichlorophosphate at 60℃; for 1h; General procedure: Acid 1 (1 mmol) and thiosemicarbazide (1.2 mmol) were added to POCl3 (1 ml), and the above mixture was stirred at 60 C for 1 h. Subsequently, the reaction solution was added into water drop by drop and Sodium hydroxide (2 M) was added to adjust the pH to 8.0, the crude product 2 was filtered off.

  • 5
  • [ 247109-15-5 ]
  • [ 56059-30-4 ]
  • [ 1233091-66-1 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 24h;
  • 6
  • [ 51226-17-6 ]
  • [ 247109-15-5 ]
  • [ 1293365-95-3 ]
YieldReaction ConditionsOperation in experiment
54% With triethylamine In 1,4-dioxane at 100℃; for 0.166667h;
  • 7
  • [ 41717-28-6 ]
  • [ 247109-15-5 ]
  • [ 1279702-34-9 ]
YieldReaction ConditionsOperation in experiment
In benzene for 0.75h;
  • 8
  • [ 1629090-01-2 ]
  • [ 247109-15-5 ]
  • [ 1629087-76-8 ]
YieldReaction ConditionsOperation in experiment
7% With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; 146 Example 146 N-[5-(3-methoxyphenyl)-l,3,4-thiadiazol-2-yl]-3-[(4-methylpiperazin-l-yl)acetyl]amino}-4- (trifluoromethoxy)benzamide To a solution of the compound of intermediate 126 (150 mg, 0.32 mmol) and 5-(3-methoxyphenyl)- l,3,4-thiadiazol-2-amine (132 mg, 0.64 mmol, 2 equiv) in DMF (2.0 mL) was added (benzotriazol-1- yloxy)tripyrrolidinophosphonium hexafluorophosphate (PYBOP, 334 mg, 0.64 mmol, 2 equiv) and diisopropylethylamine (0.28 mL, 1.60 mmol, 5 equiv). The resulting mixture was stirred at room temperature over night and was then poured into a mixture of water and ethanol (9/1). The precipitate was collected by filtration, washed with water and dried. Purification by HPLC (Waters Autopurificationsystem, column: XBrigde C18 5μιτι 100x30 mm, solvent: water / methanol + 0.2% ammonia (32%) gradient, rate: 70 mL/min, temperature: room temperature) yielded 13.0 mg (7% of theory) of the title compound. 1H-NM (300 MHz, DMSO-d6): δ [ppm] = 2.27 (s, 3H), 2.57 - 2.70 (m, 5H), 3.24 (s, 2H), 3.86 (s, 3H), 7.05 - 7.13 (m, 1H), 7.40 - 7.55 (m, 3H), 7.62 (d, 1H), 8.01 (dd, 1H), 8.97 (d, 1H), 9.92 (s, 1H), 12.86 (s, 1H). LC-MS (Method 3): Rt = 0.76 min; MS (ESIpos): m/z = 551 [M+H]+.
  • 9
  • [ 105-56-6 ]
  • [ 247109-15-5 ]
  • [ 1643337-12-5 ]
YieldReaction ConditionsOperation in experiment
78.5% With formic acid; phosphorus pentoxide
  • 10
  • [ 247109-15-5 ]
  • [ 1807313-42-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: ethanol / 18 h / Inert atmosphere; Reflux 2: tin(II) chloride dihdyrate / ethanol / 1.5 h / Inert atmosphere; Reflux
  • 11
  • [ 247109-15-5 ]
  • [ 1807313-57-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ethanol / 18 h / Inert atmosphere; Reflux 2: tin(II) chloride dihdyrate / ethanol / 1.5 h / Inert atmosphere; Reflux 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / N,N-dimethyl-formamide / 20 °C / Inert atmosphere; Cooling with ice
  • 12
  • [ 2227-64-7 ]
  • [ 247109-15-5 ]
  • [ 1807313-28-5 ]
YieldReaction ConditionsOperation in experiment
57% In ethanol for 18h; Inert atmosphere; Reflux; 10 5.1.3. General procedure B for the synthesis of compounds 3b-i, 3koand 4a-c General procedure: A mixture of the appropriate 2-amino-5-substituted 1,3,4-thiadiazole 1b-o or 4-arylthiazol-2-amine 2a-c (2 mmol) and 2-bromo-1-(3-nitrophenyl)ethanone (488 mg, 2 mmol) in anhydrousEtOH (20 mL) was stirred at reflux for 18 h. The solution wascooled to room temperature, the solvent was removed in vacuo, andsaturated aqueous NaHCO3 solution was added to make themixture basic (pH 8e9). The mixture was extracted with CH2Cl2(3 15 mL), the combined organic phases were washed with brine(10 mL) and dried with anhydrous Na2SO4. After removal of thesolvent, the residue was stirred with ethyl ether (10 mL) andfiltered to afford the desired product.
  • 13
  • [ 854382-06-2 ]
  • [ 247109-15-5 ]
  • [ 2093564-31-7 ]
YieldReaction ConditionsOperation in experiment
80.3% Stage #1: 2-((pyridin-4-ylmethyl)amino)nicotinic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.5h; Cooling with ice; Stage #2: 5-(3-methoxyphenyl)-1,3,4-thiadiazol-2-amine In N,N-dimethyl-formamide at 20℃; for 16h; Cooling with ice;
  • 14
  • [ 591-31-1 ]
  • [ 247109-15-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium acetate / water; ethanol / 0.25 h / 20 °C 2: acetic acid; iodosylbenzene; dihydrogen peroxide / dimethyl sulfoxide / 4 h / 60 °C / Green chemistry
 

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