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Chemical Structure| 13165-35-0

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Product Details of [ 13165-35-0 ]

CAS No. :13165-35-0
Formula : C8H5ClN2O2
M.W : 196.59
SMILES Code : O=C(N1)NC2=C(C=CC(Cl)=C2)C1=O
MDL No. :MFCD00563867
InChI Key :QEXAYZARVWHJJA-UHFFFAOYSA-N
Pubchem ID :246858

Safety of [ 13165-35-0 ]

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

Computational Chemistry of [ 13165-35-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 50.2
TPSA ?

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

65.72 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.17
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

1.4
Log Po/w (WLOGP)?

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

0.87
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.

1.19
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

2.84
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.49

Water Solubility

Log S (ESOL):?

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

-2.51
Solubility 0.607 mg/ml ; 0.00309 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.

-2.38
Solubility 0.812 mg/ml ; 0.00413 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

-3.76
Solubility 0.0339 mg/ml ; 0.000173 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

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.

-6.51 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

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)

1.61

Application In Synthesis of [ 13165-35-0 ]

* 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.

  • Upstream synthesis route of [ 13165-35-0 ]
  • Downstream synthetic route of [ 13165-35-0 ]

[ 13165-35-0 ] Synthesis Path-Upstream   1~13

  • 1
  • [ 124-38-9 ]
  • [ 38487-86-4 ]
  • [ 13165-35-0 ]
YieldReaction ConditionsOperation in experiment
62%
Stage #1: With 2,2'-iminobis[ethanol] In water for 0.0333333 h; Autoclave
Stage #2: at 100℃; for 12 h; Autoclave
Weigh 0.763 g (5 mmol) of 2-amino-4-chlorobenzonitrile was placed in a polytetrafluoroethylene liner of a stainless steel reactor and3 mL of a diethanolamine aqueous solution having a concentration of 1.33 mol / L was added and stirred for 2 minutes , The carbon dioxide was heated and the temperature was raisedto 100 ° C, and the carbon dioxide pressure was adjusted to 1 MPa for the carboxylation reaction under stable conditions for 12 hours.Antiupon end, the reaction system was cooled to room temperature slowly released unreacted carbon dioxide, was added 10mL of deionized water and stirreddispersion product, resulting precipitate was filtered and washed with a small amount of distilled water, and then 15mL / wash three times with methyl tert-butyl ether Andthe product was dried at a temperature of 100 ° C to give the product 7-chloroquinazoline-2,4 (1H, 3H) -dione in a yield of 62percent.
62% With {Eu[N(SiMe3)2](μ-O:κ2-C6H5C(O)NC6H3(iPr)2)(THF)}2; 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 100℃; for 24 h; In anhydrous, anaerobic, argon protection,0.0999 g (7.5 x 10-5 mol) of {L2Eu [N (SiMe3) 2] THF} 2 was added to the reaction flask,An additional 11.2 μL (7.5 × 10 -5 mol) of DBU,Under the protection of carbon dioxide bag, add 2mL dimethyl sulfoxide,Further, 0.2949 g (1.5 x 10-3 mol) of 2-amino-4-chlorobenzonitrile was added,The reaction was stirred in a constant temperature bath at 100 ° C.After 24h, add 5mL2mol / L hydrochloric acid to quench the reaction, and then suction filtered,The solid was washed with 3 × 5 mL of hydrochloric acid, then with toluene and then with diethyl ether. The residual solvent was removed and the solid was dried to give the product in 62percent yield.
References: [1] ChemSusChem, 2018, vol. 11, # 24, p. 4219 - 4225.
[2] RSC Advances, 2015, vol. 5, # 20, p. 15668 - 15673.
[3] Synthesis, 2007, # 16, p. 2524 - 2528.
[4] RSC Advances, 2015, vol. 5, # 7, p. 5032 - 5037.
[5] Green Chemistry, 2014, vol. 16, # 6, p. 3142 - 3148.
[6] Chemistry - An Asian Journal, 2016, vol. 11, # 19, p. 2735 - 2740.
[7] Tetrahedron, 2002, vol. 58, # 16, p. 3155 - 3158.
[8] Angewandte Chemie - International Edition, 2014, vol. 53, # 23, p. 5922 - 5925[9] Angew. Chem., 2014, vol. 53-126, # 23, p. 6032 - 6035.
[10] Heteroatom Chemistry, 2012, vol. 23, # 3, p. 276 - 280.
[11] Canadian Journal of Chemistry, 2019, vol. 97, # 3, p. 212 - 218.
[12] Catalysis Science and Technology, 2014, vol. 4, # 6, p. 1608 - 1614.
[13] Green Chemistry, 2013, vol. 15, # 6, p. 1485 - 1489.
[14] RSC Advances, 2014, vol. 4, # 92, p. 50993 - 50997.
[15] ChemSusChem, 2017, vol. 10, # 6, p. 1080 - 1084.
[16] Green Chemistry, 2014, vol. 16, # 1, p. 221 - 225.
[17] Tetrahedron Letters, 2004, vol. 45, # 38, p. 7073 - 7075.
[18] European Journal of Organic Chemistry, 2016, vol. 2016, # 14, p. 2555 - 2559.
[19] Patent: CN106946800, 2017, A, . Location in patent: Paragraph 0026-0027.
[20] Patent: CN105153048, 2017, B, . Location in patent: Paragraph 0130; 0131.
[21] Tetrahedron, 2010, vol. 66, # 23, p. 4063 - 4067.
[22] Inorganic Chemistry, 2012, vol. 51, # 23, p. 13001 - 13008.
[23] RSC Advances, 2016, vol. 6, # 112, p. 111079 - 111089.
  • 2
  • [ 57-13-6 ]
  • [ 89-77-0 ]
  • [ 13165-35-0 ]
YieldReaction ConditionsOperation in experiment
100% at 200℃; for 1 h; Step A:
Preparation of 7-chloro-1H-quinazoline-2,4-dione.
A mixture of 2-amino-4-chlorobenzoic acid (2.00 g, 11.6 mmol) and urea (2.80 g, 46.6 mmol) was heated to 200° C. for 1 h.
The mixture was allowed to cool to room temperature and the resulting mass was triturated well with water.
The product was collected by filtration (2.30 g, 100percent).
The MS and NMR data are in agreement with those that have been previously described: Organic Process Research and Development, 2003, 7, 700-706. 1H NMR (600 MHz, DMSO-d6): 12.00 (br s, 2H), 8.59-8.53 (m, 1H), 7.93-7.80 (m, 2H).
References: [1] Patent: US2010/204226, 2010, A1, . Location in patent: Page/Page column 22.
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 15, p. 7268 - 7274.
[3] Tetrahedron, 1997, vol. 53, # 25, p. 8457 - 8478.
[4] Patent: DE931845, 1952, , .
[5] Pharmaceutical Chemistry Journal, 1987, vol. 21, # 7, p. 478 - 483[6] Khimiko-Farmatsevticheskii Zhurnal, 1987, vol. 21, # 7, p. 802 - 807.
[7] Journal of Medicinal Chemistry, 2014, vol. 57, # 7, p. 3075 - 3093.
[8] Journal of Medicinal Chemistry, 2014, vol. 57, # 12, p. 5141 - 5156.
  • 3
  • [ 89-77-0 ]
  • [ 13165-35-0 ]
References: [1] Journal of the Chemical Society, 1948, p. 1759,1765.
[2] Patent: US5688803, 1997, A, .
[3] Chemical and Pharmaceutical Bulletin, 2014, vol. 62, # 8, p. 824 - 829.
  • 4
  • [ 38487-86-4 ]
  • [ 68-12-2 ]
  • [ 13165-35-0 ]
References: [1] Organic Process Research and Development, 2016, vol. 20, # 12, p. 2067 - 2073.
  • 5
  • [ 590-28-3 ]
  • [ 89-77-0 ]
  • [ 13165-35-0 ]
References: [1] Chinese Chemical Letters, 2012, vol. 23, # 4, p. 431 - 433.
  • 6
  • [ 214288-97-8 ]
  • [ 13165-35-0 ]
References: [1] Journal of the Chemical Society, 1948, p. 1759,1765.
[2] Organic Process Research and Development, 2003, vol. 7, # 5, p. 700 - 706.
[3] Chemical and Pharmaceutical Bulletin, 2014, vol. 62, # 8, p. 824 - 829.
  • 7
  • [ 1352572-11-2 ]
  • [ 13165-35-0 ]
References: [1] Heterocycles, 2012, vol. 85, # 11, p. 2745 - 2748,4.
[2] Heterocycles, 2012, vol. 85, # 11, p. 2745 - 2748.
  • 8
  • [ 85474-12-0 ]
  • [ 13165-35-0 ]
References: [1] Journal of Heterocyclic Chemistry, 1984, vol. 21, # 1, p. 5 - 7.
  • 9
  • [ 32315-10-9 ]
  • [ 41994-91-6 ]
  • [ 13165-35-0 ]
References: [1] Tetrahedron, 2007, vol. 63, # 39, p. 9764 - 9773.
  • 10
  • [ 38487-86-4 ]
  • [ 68-12-2 ]
  • [ 31374-18-2 ]
  • [ 13165-35-0 ]
References: [1] Organic Letters, 2009, vol. 11, # 6, p. 1193 - 1196.
  • 11
  • [ 5900-58-3 ]
  • [ 57-13-6 ]
  • [ 13165-35-0 ]
References: [1] Journal of Organic Chemistry, 1981, vol. 46, # 8, p. 1699 - 1702.
  • 12
  • [ 917-61-3 ]
  • [ 89-77-0 ]
  • [ 13165-35-0 ]
References: [1] Patent: US6344559, 2002, B1, . Location in patent: Page column 4.
  • 13
  • [ 7647-01-0 ]
  • [ 214288-97-8 ]
  • [ 13165-35-0 ]
References: [1] Journal of the Chemical Society, 1948, p. 1759,1765.
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

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