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Structure of 677304-89-1

Chemical Structure| 677304-89-1

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Product Details of [ 677304-89-1 ]

CAS No. :677304-89-1
Formula : C10H10N2O2S
M.W : 222.26
SMILES Code : O=C(C1=C(SC(N)=N2)C2=CC=C1)OCC
MDL No. :MFCD13195422
InChI Key :JJJDYTDZPDRXCF-UHFFFAOYSA-N
Pubchem ID :45076983

Safety of [ 677304-89-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 677304-89-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 9
Fraction Csp3 0.2
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 60.11
TPSA ?

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

93.45 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.12
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

2.25
Log Po/w (WLOGP)?

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

2.06
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.

1.47
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

2.57
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.09

Water Solubility

Log S (ESOL):?

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

-2.88
Solubility 0.292 mg/ml ; 0.00131 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.

-3.85
Solubility 0.0315 mg/ml ; 0.000142 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

-3.1
Solubility 0.177 mg/ml ; 0.000794 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

Yes
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.

-6.06 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)

2.43

Application In Synthesis of [ 677304-89-1 ]

* 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 [ 677304-89-1 ]

[ 677304-89-1 ] Synthesis Path-Downstream   1~6

  • 1
  • [ 677304-89-1 ]
  • (7-chlorocarbonyl-benzothiazol-2-yl)-carbamic acid <i>tert</i>-butyl ester [ No CAS ]
  • 2
  • [ 677304-89-1 ]
  • 2-<i>tert</i>-butoxycarbonylamino-benzothiazole-7-carboxylic acid [ No CAS ]
  • 3
  • [ 677304-89-1 ]
  • [7-[[(2,4,6-Trimethylphenyl)amino]carbonyl]-2-benzothiazolyl]carbamic acid, 1,1-dimethylethyl ester [ No CAS ]
  • 5
  • [ 19045-66-0 ]
  • [ 103040-92-2 ]
  • [ 677304-89-1 ]
YieldReaction ConditionsOperation in experiment
With 3-[(aminothioxomethyl)amino]benzoic acid ethyl ester; In chloroform; acetic acid; at 20 - 70℃; for 17.5h;Heating / reflux; A solution of thiocarbamate (1.95 g, 12.2 mmol, 2.11 eqiv) in chloroform (10 mL) was added dropwise over a period of 40 min to a vigorously maintained mixture of ethyl 3-[(aminocarbonothioyl)amino]benzoate (1.30 g, 5.78 mmol, 1.00 eqiv), glacial acetic acid (10 mL) and chloroform (10 mL). The mixture was maintained 30 min at rt and then was heated at 70 C for 4 h. The mixture was allowed to cool to room temperature and maintained for an additional 13 h. The volatiles were removed under reduced pressure and the solid residue was suspended in a mixture of chloroform (10 mL) and acetone (10 mL). The product was isolated by filtration, washed successively with acetone (5 mL) and hexanes (10 mL), and dried in a vacuum oven to provide 1.65 g (95%) of product as a mixture of ethyl 2-amino-1,3-benzothiazole-7-carboxylate hydrobromide and ethyl 2-amino-1,3-benzothiazole-5-carboxylate hydrobromide in a ratio of 95/5, respectively. This product was partitioned between saturated aqueous solution of sodium bicarbonate (25 mL) and a mixture of ethyl acetate (70 mL) and tetrahydrofuran (30 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was crystallized form ethyl acetate to provide pure ethyl 2-amino-1,3-benzothiazole-7-carboxylate. 1H NMR (500 MHz, DMSO-d6) & delta 1.35 (t, J= 7.5, 3H), 4.36 (q, J= 7, 2H), 7.35 (t, J= 7.5, 1H), 7.57 (d, J= 7,1H), 7.61 (bs, 2H), 7.65 (d, J= 8,1H); MS (EI) m/z 223 (M+ +1)
  • 6
  • [ 677304-86-8 ]
  • [ 677304-89-1 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In tetrahydrofuran; water; ethyl acetate; A solution of ethyl 3-aminobenzoate (90 mmol) in chlorobenzene (100 mL) was cooled to-10 C and treated with sulfuric acid (45 mmol), dropwise. After 15 min, solid potassium thiocyanate (95 mmol) was added in several portions over 30 min followed by 18-crown-6 (250 mg). The mixture was heated at 100 C for 10 h, allowed to cool to rt, and was maintained for an additional 4 h. The precipitated solids were isolated by filtration and were washed successively with chlorobenzene (25 mL) and hexanes (3 x 100 mL). The solid was suspended in water (300 mL) and the suspension was maintained 30 min. The product was isolated by filtration and washed with water (2 x 100 mL). The product was dried in a vacuum oven (55 C) for 16 h, thus providing the thiocarbamate in 69% yield.'H NMR (500 MHz, Me2SO-d6) 5 1.32 (t, J= 7.5, 3H), 4.32 (q, J = 7, 2H), 7.44-7. 47 (m, 2H), 7.68-7. 76 (m, 3H), 8.05 (s, 1H), 9. 86 (s, 1H); MS (APCI) m/z 225 (M++1). A solution of thiocarbamate (12.2 mmol) in chloroform (10 mL) was added dropwise over a period of 40 min to a vigorously maintained mixture of ethyl 3- [(aminocarbonothioyl) amino] benzoate (5.78 mmol), glacial acetic acid (10 mL) and chloroform (10 mL). The mixture was maintained 30 min at rt and then was heated at 70 C for 4 h. The mixture was allowed to cool to room temperature and maintained for an additional 13 h. The volatiles were removed under reduced pressure and the solid residue was suspended in a mixture of chloroform (10 mL) and acetone (10 mL). The product was isolated by filtration, washed successively. with acetone (5 mL) and hexanes (10 mL), and dried in a vacuum oven, thus providing the product in 95% yield as a mixture of ethyl 2-amino-1, 3-benzothiazole-7-carboxylate hydrobromide and ethyl 2-amino-1, 3- benzothiazole-5-carboxylate hydrobromide in a ratio of 95/5, respectively. This product was partitioned between saturated aqueous solution of sodium bicarbonate (25 mL) and a mixture of ethyl acetate (70 mL) and tetrahydrofuran (30 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was crystallized form ethyl acetate, thus providing pure ethyl 2-amino-1, 3-benzothiazole-7- carboxylate. 1H NMR (500 MHz, Me2SO-d6) 8 1. 35 (t, J= 7.5, 3H), 4.36 (q, J= 7,2H), 7. 35 (t, J= 7. 5, 1H), 7.57 (d, J= 7, 1H), 7.61 (bs, 2H), 7.65 (d, J= 8, 1H) ; MS (EI) mlz 223 (M++1). iso-Amylnitrite (53 mmol) was added to a solution of ethyl 2-amino-1, 3-benzothiazole-7- carboxylate (5.40 g) in tetrahydrofuran (70 mL) and the mixture was heated at reflux for 4 h. The volatiles were removed under reduced pressure and the residue was purified by chromatography (0/100 to 5/95 methanol/dichloromethane), thus providing the ester in 71% yield. lH NMR (500 MHz, CDC13) 6 1. 47 (t, J = 7. 5,3H), 4.49 (q, J= 7, 2H), 7.62 (t, J= 8, 1H), 8.20 (d, J= 6.5, 1H), 8.33 (d, J= 8, 1H), 9.12 (s, 1H); MS (EI) m/z 208 (M++1). A 50% aqueous sodium hydroxide (10 mL) was added to a 0 C solution of ethyl 1, 3-benzothiazole-7-carboxylate (16.89 mmol) in a mixture of methanol (65 mL), tetrahydrofuran (20 mL) and water (5 mL). The mixture was maintained at room temperature for 4 h and the volatiles were removed under reduced pressure. The residue was dissolved in water (100 mL) and concentrated hydrochloric acid was added to adjust the pH of the solution to 5. The mixture was cooled to 0 C and maintained for 30 min. The product was isolated by filtration, washed with water (10 mL), and dried in vacuum oven (70 C) for 16 h, thus providing the acid in 91% yield. 1H NMR (500 MHz, Me2 S O-d6) 8 7.71 (t, J = 7.5, 1H), 8.15 (d, J = 7, 1H), 8. 38 (d, J = 8, 1H), 9. 51 (s, 1H), 13.74 (bs, 1H); MS (APCI) m/z 178 (M-1).
 

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