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Chemical Structure| 1673-47-8

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Product Details of [ 1673-47-8 ]

CAS No. :1673-47-8
Formula : C7H7ClN2O
M.W : 170.60
SMILES Code : NNC(=O)C1=CC(Cl)=CC=C1
MDL No. :MFCD00014757
InChI Key :PHRDZSRVSVNQRN-UHFFFAOYSA-N
Pubchem ID :74289

Safety of [ 1673-47-8 ]

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

Computational Chemistry of [ 1673-47-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 42.35
TPSA ?

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

55.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.78
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

1.18
Log Po/w (WLOGP)?

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

0.94
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.

1.73
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

0.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.09

Water Solubility

Log S (ESOL):?

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

-1.91
Solubility 2.09 mg/ml ; 0.0122 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.

-1.93
Solubility 1.99 mg/ml ; 0.0117 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

-2.65
Solubility 0.383 mg/ml ; 0.00224 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

Yes
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.

-6.5 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

1.0
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)

1.2

Application In Synthesis of [ 1673-47-8 ]

* 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 [ 1673-47-8 ]

[ 1673-47-8 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 2905-65-9 ]
  • [ 1673-47-8 ]
YieldReaction ConditionsOperation in experiment
91.67% With hydrazine hydrate; In methanol; at 70℃; for 1h; [0283] To a stirred solution of <strong>[2905-65-9]methyl 3-chlorobenzoate</strong> (600.00 mg, 3.53 mmol) in methanol (5.00 mL) was added Hydrazine Monohydrate (1.0 mL). The resulting solution was stirred for 1 h at 70C. The precipitated solids were collected by filtration and washed with ACN (2x2 mL) to give the title compound as a off-white solid (550 mg, 91.67%) MS m/z: 171 [M+H]+.
With hydrazine hydrate; In methanol; for 5h;Reflux; General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5C.
With hydrazine hydrate; In ethanol; for 9h;Reflux; General procedure: Substituted benzoic acid (1.0 mmol) was dissolved in thionylchloride and refluxed for 2 h, then the solvent was removed underreduced pressure to obtain the white solid. The white solid in methanol was added concentrated sulfuric acid (1 mL) and themixture was refluxed for 4 h, the solvent was removed to obtaincrude solid. The crude solid was extracted with ethyl acetate andwater. The solvents were evaporated to afford the pure product.Finally, the pure product was dissolved in ethanol, and the hydrazinehydrate was added. The mixture was refluxed for 9 h, and thesolvent was removed
With hydrazine hydrate; In methanol; for 8h;Reflux; General procedure: To a solution of methyl ester of aromatic carboxylic acid 2 (0.1 mol) in methanol (30 mL), hydrazine hydrate (0.2 mol) was added drop wise with stirring. The resulting mixture was allowed to reflux for 8 h. After the completion of the reaction as monitored by TLC, the excess methanol was distilled off under reduced pressure. The resulting acid hydrazide 3 was washed with cold water, dried and recrystallized from ethanol.
With hydrazine hydrate;Reflux; General procedure: One millimole of the corresponding ester was added insmall portion to a round bottom flask containing solution ofhydrazine hydrate (10 ml) and followed by stirring themixture under reflux conditions. When completion of thereaction was monitored by TLC, the media was poured ontoice bath and the resulting precipitation was isolated by filtration.The corresponding acid hydrazide was afforded andrecrystallized from ethanol and water.
With hydrazine hydrate; In methanol; at 65℃; for 4h; General procedure: To a solution of esters (2a~2t, 1.0 equiv.), furan-2-carbonyl chloride (7a, 1.0 equiv.) orthiophene-2-carbonyl chloride (7b, 1.0 equiv.) in MeOH (2 mL/1 mmol) was added hydrazine hydrate(1 mL/1 mmol), then the mixture was allowed to reach 65 C and stirred for 4 h. After completion(monitored by TLC), the organic solvent was removed and extracted three times with ethyl acetate,the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to givethe corresponding hydrazides (3a~3t, 8a, or 8b) in high yields, which were taken up for the next stepwithout any purification.
With hydrazine hydrate; In methanol;Reflux; Inert atmosphere; General procedure: Hydrazine hydrate (5 mL, 40%) was added to a solution of requiredester (5.0 mmol) in methanol (20 mL). The solution was refluxed for12-24 h and monitored by TLC until starting material was completelyconsumed. After that, solvent was evaporated under reduced pressureand a small amount of water (5 mL) was added to precipitate the hydrazide,which was filtered and dried in vacuum to give a shiny white toyellow solid in excellent yields, without further purification.
With hydrazine hydrate; In methanol; at 80℃; for 4h; General procedure: At the 250 cm3double-mouth bottle, 13.5 mmol of themethyl benzoate derivatives was added to 100 cm3of methanol,added 6.75 cm3of hydrazine hydrate (108 mmol) tothe reaction mixture slowly. After that warming to 80 Cand reflux for 4 h until the reaction was completed, thenconcentrated under reducing pressure to remove methanol,filtering and drying to get white solid 2.
With hydrazine hydrate; In ethanol;Reflux; General procedure: Method A Methyl benzoate derivatives (2, 1 eq) and 85% hydrazine hydrate (10 eq) were dissolved in ethanol (45 mL). The mixture was refluxed overnight. After cooling, the solvent was removed in vacuo and the residue was separated on the Biotage SNAP Cartridge KP-Sil 100 g eluting with 0-60 % ethyl acetate/petroleum ether to afford compound 4.

References: [1]Biomedicine and Pharmacotherapy,2017,vol. 94,p. 499 - 513.
[2]Patent: WO2021/231565,2021,A1 .Location in patent: Paragraph 0283; 0275.
[3]Letters in drug design and discovery,2012,vol. 9,p. 276 - 281.
[4]Journal of Medicinal Chemistry,2016,vol. 59,p. 2362 - 2380.
[5]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 6724 - 6731.
[6]Zeitschrift fur Naturforschung, B: Chemical Sciences,2010,vol. 65,p. 178 - 184.
[7]European Journal of Medicinal Chemistry,2010,vol. 45,p. 5200 - 5207.
[8]Monatshefte fur Chemie,2010,vol. 141,p. 479 - 484.
[9]Oriental Journal of Chemistry,2011,vol. 27,p. 1465 - 1473.
[10]Arzneimittel-Forschung/Drug Research,2011,vol. 61,p. 452 - 457.
[11]Medicinal Chemistry,2012,vol. 8,p. 1190 - 1197,8.
[12]Chemical Biology and Drug Design,2013,vol. 82,p. 546 - 556.
[13]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 192 - 194.
[14]Medicinal Chemistry Research,2014,vol. 23,p. 1661 - 1671.
[15]Synthetic Communications,2014,vol. 44,p. 2724 - 2737.
[16]Chemical Communications,2015,vol. 51,p. 14365 - 14368.
[17]Journal of Molecular Structure,2016,vol. 1117,p. 8 - 16.
[18]Molecules,2016,vol. 21.
[19]Letters in drug design and discovery,2016,vol. 13,p. 968 - 981.
[20]Journal of the Chemical Society of Pakistan,2016,vol. 38,p. 864 - 881.
[21]Chemical Biology and Drug Design,2017,vol. 89,p. 47 - 60.
[22]Arkivoc,2016,vol. 2017,p. 87 - 106.
[23]Journal of Medicinal Chemistry,2019,vol. 62,p. 4350 - 4369.
[24]Medicinal Chemistry Research,2020,vol. 29,p. 341 - 355.
[25]Molecules,2020,vol. 25.
[26]Bioorganic Chemistry,2020,vol. 96.
[27]Australian Journal of Chemistry,2012,vol. 65,p. 1413 - 1419,7.
[28]Bioorganic Chemistry,2020,vol. 104.
[29]Monatshefte fur Chemie,2021,vol. 152,p. 121 - 135.
[30]Bioorganic Chemistry,2021,vol. 110.
[31]Journal of Enzyme Inhibition and Medicinal Chemistry,2021,vol. 36,p. 1093 - 1114.
  • 2
  • [ 103854-64-4 ]
  • [ 1673-47-8 ]
  • C18H14ClN3O2 [ No CAS ]
 

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