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Chemical Structure| 5922-60-1

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Product Details of [ 5922-60-1 ]

CAS No. :5922-60-1
Formula : C7H5ClN2
M.W : 152.58
SMILES Code : C1=C(Cl)C=CC(=C1C#N)N
MDL No. :MFCD00017106
InChI Key :QYRDWARBHMCOAG-UHFFFAOYSA-N
Pubchem ID :80019

Safety of [ 5922-60-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H312-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 5922-60-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 40.57
TPSA ?

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

49.81 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

2.55
Log Po/w (WLOGP)?

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

1.8
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.

1.39
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

1.72
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.79

Water Solubility

Log S (ESOL):?

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

-2.84
Solubility 0.222 mg/ml ; 0.00146 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.

-3.24
Solubility 0.0871 mg/ml ; 0.000571 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

-2.72
Solubility 0.289 mg/ml ; 0.00189 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

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.

-5.42 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

1.0 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)

1.36

Application In Synthesis of [ 5922-60-1 ]

* 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 [ 5922-60-1 ]
  • Downstream synthetic route of [ 5922-60-1 ]

[ 5922-60-1 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 124-38-9 ]
  • [ 5922-60-1 ]
  • [ 1640-60-4 ]
YieldReaction ConditionsOperation in experiment
99% With tetrabutyl ammonium fluoride In dimethyl sulfoxide at 110℃; for 24 h; Autoclave General procedure: Table 5: To a DMSO‑d6 solution (1 mL) of 2-aminobenzonitrile 4a (1 mmol) in a stainless steel autoclave was added a catalyst (0.01 mmol) under an argon atmosphere. The autoclave was sealed, heated at 110°C and then pressurized with CO2 of 2 MPa. The cyclization reaction of 4a proceeded by the magnetic stirring of the resulting mixture at 110°C for 3 h. After the reaction the autoclave was cooled in an ice bath and depressurized. The chemical yield of quinazoline-2,4(1H,3H)-dione 5a was determined by integrating 1HNMR with reference to an internal standard (3,5-dimethoxybenzylalcohol), which was added to the reaction mixture. Table 6: DMSO solution (6 mL) of 4 (6 mmol) was treated for the carboxylative cyclization of 4 with CO2 according to the procedure of Table 5. After the reaction, the autoclave was cooled in an ice bath and depressurized, and the reaction mixture was added to water (60 mL). The precipitation was collected by filtration, washed with water and diethyl ether, and then dried in vacuo at 35°C for 15 h to give the pure product 5.
94% With fibrous nanosilica functionalized with sodium tripolyphosphate and 3-aminopropyltriethoxysilane In neat (no solvent) at 70℃; for 0.833333 h; Autoclave; Green chemistry General procedure: 2-aminobenzonitrile (1 mmol) and KCC-1/STPP NPs (0.7 mg) were mixed together. The autoclave was closed, purged twice with CO2 gas, pressurized to 1.5 MPa of CO2, and heated at 70°C for 50 min. Then, the reactor was cooled to ambient temperature and the resulting mixture was transferred to a 50 mL round-bottom flask. During completion, the reaction progress was monitored by TLC. Following its completion, EtOH was added to the reaction mixture and the catalyst was separated by filtration. Afterwards, the solvent was removed from the solution under reduced pressure and the resulting product was purified by recrystallization using n-hexane/ethyl acetate. The products are known and their sample characterization data is presented in the Supplemental Materials.
93%
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-5-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 6-chloroquinazoline-2,4 (1H, 3H) -dione having a yield of 93percent.
92% at 70℃; for 1 h; Autoclave General procedure: 2-aminobenzonitrile (1mmol), and KCC-1/IL NPs (0.0007g) were added. The autoclave was closed, purged twice with CO2 gas, pressurized with 0.8MPa of CO2 and then heated at 70°C for 60min. Then the reactor was cooled to ambient temperature, and the resulting mixture was transferred to a 50mL round bottom flask. Upon completion, the progress of the reaction was monitored by TLC when the reaction was completed, EtOH was added to the reaction mixture and the KCC-1/IL NPs were separated by distillation under vacuum. Then the solvent was removed from solution under reduced pressure and the resulting product purified by recrystallization using n-hexane/ethyl acetate.
91% 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) DBU was added, under the protection of carbon dioxide bag,Add 2 mL of dimethyl sulfoxide, add 0.2949 g (1.5 × 10 -3 mol) of 2-amino-5-chlorobenzonitrile,The reaction was stirred in a constant temperature bath at 100 ° C. After 24h, add 5mL 2mol / L hydrochloric acid to quench the reaction,Suction filtration, successively washed with 3 × 5mL hydrochloric acid, toluene and ether solids, the residual solvent was stripped, dried solids,The product was obtained in 91percent yield.

References: [1] Heteroatom Chemistry, 2012, vol. 23, # 3, p. 276 - 280.
[2] RSC Advances, 2015, vol. 5, # 7, p. 5032 - 5037.
[3] Tetrahedron, 2018, vol. 74, # 24, p. 2914 - 2920.
[4] Green Chemistry, 2014, vol. 16, # 6, p. 3142 - 3148.
[5] ChemSusChem, 2018, vol. 11, # 24, p. 4219 - 4225.
[6] Tetrahedron, 2002, vol. 58, # 16, p. 3155 - 3158.
[7] Synthesis, 2007, # 16, p. 2524 - 2528.
[8] Tetrahedron Letters, 2004, vol. 45, # 38, p. 7073 - 7075.
[9] Angewandte Chemie - International Edition, 2012, vol. 51, # 27, p. 6700 - 6703.
[10] RSC Advances, 2015, vol. 5, # 20, p. 15668 - 15673.
[11] Tetrahedron, 2010, vol. 66, # 23, p. 4063 - 4067.
[12] Inorganic Chemistry, 2012, vol. 51, # 23, p. 13001 - 13008.
[13] Catalysis Science and Technology, 2016, vol. 6, # 5, p. 1435 - 1441.
[14] Phosphorus, Sulfur and Silicon and the Related Elements, 2018, vol. 193, # 8, p. 535 - 544.
[15] Patent: CN106946800, 2017, A, . Location in patent: Paragraph 0022-0023.
[16] Angewandte Chemie - International Edition, 2014, vol. 53, # 23, p. 5922 - 5925[17] Angew. Chem., 2014, vol. 53-126, # 23, p. 6032 - 6035.
[18] Catalysis Communications, 2015, vol. 72, p. 91 - 96.
[19] Chemistry - An Asian Journal, 2016, vol. 11, # 19, p. 2735 - 2740.
[20] Green Chemistry, 2014, vol. 16, # 1, p. 221 - 225.
[21] RSC Advances, 2014, vol. 4, # 92, p. 50993 - 50997.
[22] European Journal of Organic Chemistry, 2016, vol. 2016, # 14, p. 2555 - 2559.
[23] Patent: CN105153048, 2017, B, . Location in patent: Paragraph 0126; 0127.
[24] Canadian Journal of Chemistry, 2019, vol. 97, # 3, p. 212 - 218.
[25] RSC Advances, 2015, vol. 5, # 31, p. 24670 - 24674.
[26] Green Chemistry, 2013, vol. 15, # 6, p. 1485 - 1489.
[27] Catalysis Science and Technology, 2014, vol. 4, # 6, p. 1608 - 1614.
[28] ChemCatChem, 2016, vol. 8, # 1, p. 244 - 250.
[29] ChemSusChem, 2017, vol. 10, # 6, p. 1145 - 1151.
[30] RSC Advances, 2016, vol. 6, # 112, p. 111079 - 111089.
  • 2
  • [ 5922-60-1 ]
  • [ 68-12-2 ]
  • [ 1640-60-4 ]
References: [1] Organic Process Research and Development, 2016, vol. 20, # 12, p. 2067 - 2073.
  • 3
  • [ 5922-60-1 ]
  • [ 68-12-2 ]
  • [ 16064-14-5 ]
  • [ 1640-60-4 ]
References: [1] Organic Letters, 2009, vol. 11, # 6, p. 1193 - 1196.
  • 4
  • [ 5922-60-1 ]
  • [ 77287-34-4 ]
  • [ 19808-35-6 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: at 180℃; for 6 h;
Example 4 - synthesis of 4-amino-6-chloro-quinazolineA solution of 2-amino-5-chlorobenzonitrile (1.07 g, 7.0 mmol) in formamide (20 ml) was heated at 180 0C for 6 hours. After cooling to room temperature, water (30 ml) was added to the reaction mixture. The precipitate was collected by filtration, washed with water and dried over P2O5, yielding the title compound as a grey solid (1.2 g, yield: 95 percent) which was characterized by its mass spectrum as follows: MS (m/z): 180 ([M+H]+, 100).
95% at 180℃; for 6 h; Example 4 - synthesis of 4-amino-6-chloro-quinazoline; A solution of 2-amino-5-chlorobenzonitrile (1.07 g, 7.0 mmol) in formamide (20 ml) was heated at 180 0C for 6 hours. After cooling to room temperature, water (30 ml) was added to the reaction mixture. The precipitate was collected by filtration, washed with water and dried over P2O5, yielding the title compound as a grey solid (1.2 g, yield: 95 percent) which was characterized by its mass spectrum as follows: MS (m/z): 180 ([M+H]+, 100).
References: [1] Patent: WO2008/9077, 2008, A2, . Location in patent: Page/Page column 61.
[2] Patent: WO2008/9078, 2008, A2, . Location in patent: Page/Page column 60.
  • 5
  • [ 5922-60-1 ]
  • [ 3473-63-0 ]
  • [ 19808-35-6 ]
References: [1] Journal of Heterocyclic Chemistry, 2011, vol. 48, # 6, p. 1407 - 1413.
 

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