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Chemical Structure| 100784-27-8 Chemical Structure| 100784-27-8

Structure of 100784-27-8

Chemical Structure| 100784-27-8

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Product Details of [ 100784-27-8 ]

CAS No. :100784-27-8
Formula : C6H8ClN3O4S
M.W : 253.66
SMILES Code : COC(=O)C1=C(N(C)N=C1Cl)S(N)(=O)=O
MDL No. :MFCD13152198
InChI Key :PVZNZXMAJKZBCU-UHFFFAOYSA-N
Pubchem ID :10587002

Safety of [ 100784-27-8 ]

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

Computational Chemistry of [ 100784-27-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 3
Num. H-bond acceptors 6.0
Num. H-bond donors 1.0
Molar Refractivity 50.77
TPSA ?

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

112.66 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.95
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

-0.05
Log Po/w (WLOGP)?

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

0.59
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.

-0.93
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

-0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.06

Water Solubility

Log S (ESOL):?

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

-1.43
Solubility 9.43 mg/ml ; 0.0372 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.87
Solubility 3.46 mg/ml ; 0.0136 mol/l
Class?

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

Very 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

-1.06
Solubility 22.0 mg/ml ; 0.0869 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

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

No
Log Kp (skin permeation)?

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

-7.88 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<0.0
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)

2.62

Application In Synthesis of [ 100784-27-8 ]

* 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 [ 100784-27-8 ]

[ 100784-27-8 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 89392-03-0 ]
  • [ 100784-27-8 ]
  • halosulfuron methyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With triethylamine; In acetonitrile; at 60.0℃; for 0.166667h;Microwave irradiation; A mixture of compound 6 (0.32 g, 1.16 mmol), compound 4 (0.25 g, 0.98 mmol) and triethylamine (0.12 g, 1.18 mmol) in acetonitrile (5 mL) was irradiated in a microwave at 60 C for 10 min. After completion of the reaction (checked by TLC), the reaction mixture was diluted with water (10 mL) and extracted with dichloromethane (10 mL). The organic layer was washed with 1 M HCl (2 × 5 mL) and then with water (20 mL) followed by brine solution (10 mL). The organic layer was dried over anhydrous sodium sulphate (6.2 g), filtered and evaporated under reduced pressure to obtain the crude product. The crude product was re-crystallized in acetonitrile (10 mL) to obtain the pure compound 7. Off-white powder; Yield: 0.410 g, 96 %; m.p.: 176 C (Lit. m.p.: 175.5-177.2 C); 1H NMR (400 MHz, CDCl3): delta 7.56 (s, 1H), 5.64 (s, 1H), 4.17 (s, 1H), 3.86 (s, 6H), 3.71 (s, 3H); ESI-MS: m/z,435.1 (M+1)+.
  • 3
  • [ 88398-85-0 ]
  • [ 100784-27-8 ]
  • 6
  • [ 148934-66-1 ]
  • [ 100784-27-8 ]
YieldReaction ConditionsOperation in experiment
REFERENCE EXAMPLE 2 Synthesis of 3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide Following the procedure as described in Reference example 1, 3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide was synthesised. m.p.: 125-126 C. Intermediate compound: 3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonyl chloride. b.p.: 123 C./0.25 mmHg.
  • 9
  • halosulfuron methyl [ No CAS ]
  • [ 1048337-28-5 ]
  • [ 100784-27-8 ]
  • 10
  • [ 100784-27-8 ]
  • 3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide isocyanate [ No CAS ]
  • 11
  • [ 100784-27-8 ]
  • halosulfuron methyl [ No CAS ]
  • 12
  • [ 111-36-4 ]
  • [ 100784-27-8 ]
  • N-(n-butylcarbamoyl)-3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
5.2 g With potassium carbonate; In acetone; for 3.0h;Reflux; To a mixture of <strong>[100784-27-8]3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide</strong> (7.0 g), 5.3 g anhydrous potassium carbonate and 50 ml of dry acetone, 2.8 g of n-butyl isocyanate was added at room temperature. The mixture was refluxed for 3 hours. (0092) After refluxing, acetone was evaporated under reduced pressure and the residue was dissolved in ice-water. After separation of a trace of water insolubles, the filtrate was acidified with hydrochloric acid and the crystals formed were filtered, washed with water and dried to obtain 5.2 g N-(n-butylcarbamoyl)-<strong>[100784-27-8]3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide</strong>.
With potassium carbonate; In toluene; for 3.0h;Reflux; To a mixture of 7.0 g of <strong>[100784-27-8]3-chloro-4-methoxycarbonyl-1-methylpyrazole-5-sulfonamide</strong>, 5.3 g of anhydrous potassium carbonate and 50 ml of dry acetone there was added 2.8 g of n-butyl isocyanate at room temperature, and the mixture was refluxed for 3 hours. After the reaction, acetone was evaporated under reduced pressure and the residue was dissolved in ice-water. After separation of a trace of water insolubles, the filtrate was made acidic with hydrochloric acid and the crystals formed were filtered, washed with water and dried to give 5.2 g of N-(n-butylcarbamoyl)-3-chloro-4-methoxycarbonyl-1-methlpyrazole-5-sulfonamide. (0065) Into a mixture of 120 ml of dry toluene and the product obtained from the above procedure, 4.2 g of phosgene was passed under reflux. Then, the reaction mixture was further refluxed for 1.5 hours. After completion of the reaction, evaporation under reduced pressure to obtain crude 3-chloro-4-ethoxycarbonyl-1-methylpyrazole-5-sulfonyl isocyanate.
  • 13
  • methyl 3-chloro-5-hydroxy-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 100784-27-8 ]
  • 14
  • methyl 3-chloro-5-[(dimethylcarbamothioyl)oxy]-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 100784-27-8 ]
  • 15
  • methyl 3-chloro-5-(chlorosulfonyl)-1-methyl-1H-pyrazole-4-carboxylate [ No CAS ]
  • [ 100784-27-8 ]
YieldReaction ConditionsOperation in experiment
95.1% With ammonium hydroxide; at 50.0℃; for 2.0h; The combined dichloromethane layer was added to the reaction apparatus, was added 28wt% aqueous ammonia 250g (2mol), at 50 Amination reaction temperature 2h.After the reaction, after washing, centrifuging and drying, 120.5 g of chloropyrazole sulfonamide was obtained with a purity of 98.0% and a yield of95.1% [Step 3 of 3-chloro-1-methylpyrazole-5-dimethylaminothiocarbonyloxy-4-carboxylic acid methyl ester].
4.41 g With ammonium carbonate; In acetonitrile; at 20.0℃; To a stirred mixture of compound 3 (4 g, 19.35 mmol), tetrabutylammonium chloride (21.5 g, 77.36 mmol) and water (0.87 g, 48.33 mmol) in MeCN (25 mL) at 0 C, N-chlorosuccinimide (7.75 g, 58.04 mmol) was added as a solid in portions over 1-2 min. After 30 min, ammonium carbonate (1.95 g, 20.30 mmol) was added to the mixture over 1-2 min. The resulting mixture was stirred at room temperature for 12 h (until TLC showed complete disappearance of starting material). The mixture was filtered and rinsed with acetonitrile (20 mL). The filtrate was evaporated to obtain compound 4. Recrystallization from a mixture of EtOH and water resulted in pure product. White solid, Yield: 4.41 g, 90 %; m.p.: 125-126 C; 1H NMR (DMSO-d6, 300 MHz): delta 8.10 (brs, 2H, NH2), 4.05 (s, 3H, NMe), 3.88 (s, 3H); ESI-MS: m/z, 254 (M+1).
 

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