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Structure of 859877-49-9

Chemical Structure| 859877-49-9

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Product Details of [ 859877-49-9 ]

CAS No. :859877-49-9
Formula : C7H7ClN2O3
M.W : 202.60
SMILES Code : NC1=C([N+]([O-])=O)C=C(Cl)C=C1OC
MDL No. :MFCD28405560
InChI Key :MQNYHIKKJRBLTG-UHFFFAOYSA-N
Pubchem ID :59644362

Safety of [ 859877-49-9 ]

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

Computational Chemistry of [ 859877-49-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 51.17
TPSA ?

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

81.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.48
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

2.22
Log Po/w (WLOGP)?

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

1.85
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.

0.65
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

-0.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.16

Water Solubility

Log S (ESOL):?

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

-2.7
Solubility 0.4 mg/ml ; 0.00198 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.

-3.56
Solubility 0.0561 mg/ml ; 0.000277 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

-2.17
Solubility 1.37 mg/ml ; 0.00678 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

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.

-5.96 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

3.0 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)

2.37

Application In Synthesis of [ 859877-49-9 ]

* 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 [ 859877-49-9 ]

[ 859877-49-9 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 16554-45-3 ]
  • [ 859877-49-9 ]
YieldReaction ConditionsOperation in experiment
With N-chloro-succinimide; In acetonitrile; at 20 - 60℃; for 18h;Heating / reflux; To a solution of the title compound of Example 21, Step A (26.6 mmol, 4.5 g) in MeCN (30 mL) at 60 C was added N-chlorosuccinimide (29 mmol, 3.9 g). The solution was brought to reflux for 2 h and allowed to stand at ambient temperature for 16 h. The reaction mixture was partitioned between CH2C12 and saturated NaHC03. The organic phase was washed with brine, dried with Na2SO4, and concentrated in vacuo to afford the product as a brown solid. LC-MS (ESI, Method B): 2.14 min, m/z 203.11 (M + 1).
YieldReaction ConditionsOperation in experiment
3.05 g (69%) Step 2. 4-Chloro-2-methoxy-6-nitrophenylamine. Aniline 136 from the previous step (3.74 g, 22.2 mmol) was dissolved in acetonitrile (100 ml) and N-chlorosuccinimide (3.07 g, 23 mmol) was added. The mixture was heated under reflux overnight then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give product 137 as orange needles 3.05 g (69%).
  • 3
  • [ 859877-49-9 ]
  • [ 6303-21-5 ]
  • [ 55910-07-1 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; sodium nitrite; In water; acetic acid; Step 3. 1-chloro-3-methoxy-5-nitrobenzene. 4-Chloro-2-methoxy-6-nitroaniline (137) (14 g, 69 mmol) was dissolved in glacial acetic acid (115 ml) and treated with concentrated sulfuric acid (110 ml). The solution was cooled in an ice bath and a cold solution of sodium nitrite (5.03 g, 73 mmol) in water (20 ml) was added slowly to keep the reaction temperature below 5 C. After the addition was complete, the reaction was stirred for an additional 15 minutes before the addition of hypophosphorous acid (70 ml of a 50% solution in water, 0.9 M). The mixture was stirred at room temperature overnight and recooled with an ice bath. The solids were collected by filtration, washed with water, then dried under vacuum to give 3-chloro-5-nitro anisole (138) as a light salmon-colored solid 7.43 g, 57%).
  • 4
  • [ 859877-49-9 ]
  • [ 74-88-4 ]
  • [ 859877-50-2 ]
YieldReaction ConditionsOperation in experiment
To the title compound of Example 21, Step B (19.9 mmol, 4.03 g) in DMF (50 mL) at 0 C was added portionwise NaH (31.8 mmol, 1.27 g of 60% suspension in mineral oil) (exothermic, gas evolution). After 10 min MeI (23 mmol, 1.5 mL) was added and the reaction was allowed to stand at ambient temperature for 3 h. Saturated NaHC03 and brine were added to the reaction resulting in formation of a precipitate, which was filtered, washed with water and dried in vacuo. Flash chromatography on silica eluting with 15% EtOAc in hexanes afforded the product as a bright red solid. LC-MS (ESI, Method B): 2.31 min, m/z 217.2 (M + 1).
  • 5
  • [ 859877-49-9 ]
  • 2-amino-5(6)-chloro-7(4)-hydroxybenzimidazole hydrobromide [ No CAS ]
  • 6
  • [ 859877-49-9 ]
  • [ 1255789-24-2 ]
YieldReaction ConditionsOperation in experiment
93% With iron; ammonium chloride; In ethanol; water; for 4h;Reflux; Step 3. 5-Chloro-3-meihoxybenzene-l,2-diamine. A mixture of 4-chloro-2- methoxy-6-nitroaniline (1.01 g, 5 mmol), Fe (1.68 g, 30 mmol), and NH4CI (2.67g, 50 mmol) in EtOH (10 mL) and water (5 mL) was stirred at reflux for 4hr and then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography to give 5-chloro-3-methoxybenzene-l,2-diamine (0.80 g, 93% yield) as brown solid. LC-MS: m/z 173 (M+H)+.
  • 7
  • [ 859877-49-9 ]
  • 2-amino-5(6)-chloro-7(4)-methoxybenzimidazole hydrobromide [ No CAS ]
  • 8
  • [ 924274-94-2 ]
  • [ 74-88-4 ]
  • [ 859877-49-9 ]
YieldReaction ConditionsOperation in experiment
46.4% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h; Step 2. 4-Chloro-2-methoxy-6-nitroaniline. To a mixture of 2-amino-5- chloro-3-nitrophenol (752 mg, 4.0 mmol) and potassium carbonate (415 mg, 3.0 mmol) in DMF was added Mel (625 mg, 4.4 mmol). The reaction mixture was stirred at r.t. for 2hr, then quenched with water and extracted with EtOAc. Combined organic layers were washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography to give 4-chloro-2- methoxy- 6-nitroaniline (450 mg, 46.4% yield). LC-MS: m/z 203(M-H)+.
  • 9
  • [ 603-85-0 ]
  • [ 859877-49-9 ]
  • 10
  • [ 859877-49-9 ]
  • 2-(5-chloro-7-methoxy-1H-benzo[d]imidazol-2-ylthio)-N-(4-(pyridin-3-yloxy)phenyl)acetamide [ No CAS ]
  • 11
  • [ 859877-49-9 ]
  • 5-chloro-7-methoxy-1H-benzo[d]imidazole-2-thiol [ No CAS ]
  • 12
  • [ 859877-49-9 ]
  • (1-(4-chloro-2-methoxy-6-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl 2-(4-oxo-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-3(4H)-yl)acetate [ No CAS ]
  • 13
  • [ 859877-49-9 ]
  • C7H5ClN4O3 [ No CAS ]
 

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