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Structure of 247037-82-7

Chemical Structure| 247037-82-7

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Product Details of [ 247037-82-7 ]

CAS No. :247037-82-7
Formula : C4H6ClN3S
M.W : 163.63
SMILES Code : N=C(C1=NC=CS1)N.[H]Cl
MDL No. :MFCD18651714
InChI Key :MOIIOZOJYWYXEP-UHFFFAOYSA-N
Pubchem ID :18679584

Safety of [ 247037-82-7 ]

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

Computational Chemistry of [ 247037-82-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 40.34
TPSA ?

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

91.0 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

1.05
Log Po/w (WLOGP)?

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

1.23
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.

-0.36
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

1.45
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.67

Water Solubility

Log S (ESOL):?

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

-1.86
Solubility 2.25 mg/ml ; 0.0138 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.

-2.55
Solubility 0.459 mg/ml ; 0.00281 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

-0.99
Solubility 16.8 mg/ml ; 0.103 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.

-6.55 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

2.0
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

2.0 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 [ 247037-82-7 ]

* 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 [ 247037-82-7 ]

[ 247037-82-7 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 247037-82-7 ]
  • [ 105-45-3 ]
  • [ 90176-80-0 ]
  • C17H13F4N3O2S [ No CAS ]
  • 2
  • [ 67482-48-8 ]
  • [ 247037-82-7 ]
  • [ 630128-01-7 ]
  • C21H23ClN4O6S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% With sodium hydrogencarbonate; In N,N-dimethyl-formamide; at 60℃; for 4h;Inert atmosphere; Step 1 (Synthesis of 177-4) (0846) Compound 177-1 (3.86 g, 26.36 mmol, 1.0 eq.), 177-2 (10.0 g, 26.36 mmol, 1.0 eq.), 177-3 (4.31 g, 26.36 mmol, 1.0 eq.) were dissolved in anhydrous DMF (100 mL), and at 20 C. was added NaHCO3 (8.86 g, 105.44 mmol, 4.00 eq). After the addition, the reaction mixture was swept with nitrogen for 3 times, the mixture was warmed to 60 C., and stirred for 4 hours. The reaction mixture was cooled to room temperature, and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with water (100 mL), and then extracted with EtOAc (100 mL) for 3 times. (0847) The organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatograph with an eluent system of DCM/MeOH=20/1, 10/1, to obtain 11 g product as yellow oil, yield: 66%. (0848) LCMS (ESI) m/z: 527.1 [M+H+].
  • 3
  • [ 247037-82-7 ]
  • [ 161793-17-5 ]
  • [ 630128-01-7 ]
  • C23H23F3N4O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 4-methyl-morpholine; In tetrahydrofuran; at 60℃; for 20h;Large scale; Compound 4 (1140 g, 3 mol) and anhydrous THF(7.5 L) were added to a 30 L jacketed reaction flask and stirred. Compound 6 (566 g, 3.45 mol), Compound 7 (502 g,1.1 mol) and NMM (760 g, 7.5 mol) were added. The reaction was refluxed (60 C.) for 20 h. The content of the intermediate carboxylic acid was monitored by HPLC and the temperature was cooled to 5-10 C. The isobutyl chloroformate (492 g, 3.6 mol, dissolved in 500 mE THF) was added dropwise and reacted at 5-10 C. for 1 h. TEC and HPEC showed that the intermediate carboxylic acid of the reaction was reacted completely. The reaction was quenched by the addition of H20 (3 E), and extracted with EtOAc (9 E), and the organic solvent was washed once with H20 (3 E) and concentrated to give 2.2 kg of mother liquor. The mother liquor was dissolved in EtOAc (3 E), THF (500 mE) was added, n-heptane (about 9 E) was slowly added dropwise and the mixture was stirred at 15 C. overnight with a solid precipitated, and filtered to give a crude solid with a purity of 95%, De=85%. Recrystallization of the crude product:The solid was dissolved in THF/EtOAc (100 g in 500/500 mE) at 50 C., added dropwise with n-heptane (1 E) and stirred for 1 h, then gradually cooled to 25 C. and stirred overnight, filtered to give Compound 9A as a white solid (500 g, purity: 96%, De>96%, yield: 27%).
  • 4
  • [ 247037-82-7 ]
  • [ 161793-17-5 ]
  • [ 630128-01-7 ]
  • C23H21F3N4O5S [ No CAS ]
YieldReaction ConditionsOperation in experiment
27.1% Compound 4 (1140 g, 3 mol) and anhydrous THF (7.5 L) were added to a 30 L reaction flask and stirred. Compound 5 (566 g, 3.45 mol), compound 6 (502 g, 1.1 mol) and N-methylmorpholine (760 g, 7.5 mol) were added. The reaction solution was refluxed (60 C.) for 20 hours, cooled to 5 C. to 10 C., added with isobutyl chloroformate (492 g, 3.6 mol, dissolved in 500 mL THF) dropwise, and reacted at 5 C. to 10 C. for 1 hour. After the intermediate carboxylic acid was completely reacted, the reaction was quenched by the addition of water (3 L). Ethyl acetate (9 L) was added for extraction and the organic phase was washed with water (3 L) once, concentrated to give a mother liquor of 2.2 kg. The mother liquid was dissolved in ethyl acetate (3 L), added with tetrahydrofuran (500 mL), slowly added dropwise within-heptane (about 9 L), and stirred at 15 C. overnight to precipitate a solid. The solid was recrystallized from tetrahydrofuran/ethyl acetate/n-heptane solvent system (5 mL/5 mL/10 mL/g) to obtain 500 g compound 8A, of which the purity reached 96%, ee value>96% and yield was 27.1%.
 

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