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Chemical Structure| 680210-85-9 Chemical Structure| 680210-85-9

Structure of 680210-85-9

Chemical Structure| 680210-85-9

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Product Details of [ 680210-85-9 ]

CAS No. :680210-85-9
Formula : C10H5ClN2O
M.W : 204.61
SMILES Code : N#CC1=C(Cl)C2=C(NC1=O)C=CC=C2
MDL No. :MFCD01570117
InChI Key :JWBMUCZTOBYSEM-UHFFFAOYSA-N
Pubchem ID :2777510

Safety of [ 680210-85-9 ]

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

Computational Chemistry of [ 680210-85-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 54.29
TPSA ?

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

56.65 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.53
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

1.61
Log Po/w (WLOGP)?

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

2.05
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.

1.55
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

3.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.98

Water Solubility

Log S (ESOL):?

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

-2.65
Solubility 0.457 mg/ml ; 0.00223 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.

-2.41
Solubility 0.793 mg/ml ; 0.00388 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

-4.32
Solubility 0.00988 mg/ml ; 0.0000483 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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.

-6.41 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

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)

1.76

Application In Synthesis of [ 680210-85-9 ]

* 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 [ 680210-85-9 ]

[ 680210-85-9 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 680210-85-9 ]
  • [ 52063-83-9 ]
  • 2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-quinoline-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% In toluene; at 110℃; PIPERAZINE-1-YL-THIOPHEN-2-YL-METHANONE (8.0 g, 41 mmol) was added to a solution of Compound 115 (4.1 g, 20 mmol) in toluene (50 mL) and heated overnight at 110 C. The solvent was removed under vacuum. The residue was suspended in water, sonicated, and filtered. The crude product was purified by flash chromatography eluting with 0-2% methanol in dichloromethane gradient to yield 6.4 g (88%) of white solids. M. P. 264 C. LH NMR (DMSO-d6): d 3.7 (m, 4H), 3.9 (m, 4H), 7.16 (t, J= 4.8 Hz, 1H), 7.23 (t, J= 5.9 Hz, 1H), 7.31 (d, J= 8.6 Hz, 1H), 7.49 (d, J= 4.0 Hz, 1H), 7.61 (t, J= 8.3 Hz, 1H), 7.8 (m, 2H), 11.90 (b, 1H) ; EIMS: 364 (M+H).
  • 2
  • [ 69875-54-3 ]
  • [ 680210-85-9 ]
YieldReaction ConditionsOperation in experiment
94% With ammonium acetate; acetic acid; at 140℃; for 4h; Ammonium acetate (2.1 g, 27 mmol) was added to a suspension of Compound 114 (6.0 g, 27 mmol) in glacial acetic acid and heated at 140 C for 4 h. The solution was cooled and poured into ice water. The solids formed were filtered, washed by water, and dried under vacuum to yield 5.2 g (94%) of white solids. M. P. 302C. 1H NMR (DMSO-DS) : d 1H-NMR (DMSO-d6): 7. 4 (m, 2H), 7.79 (T, J= 7.6 Hz, 1H), 7.96 (d, J= 8. 0 Hz, 1H), ; EIMS : 205 (M+H).
77% With ammonium acetate; acetic acid; at 140℃; for 4h; 2,4-dichloroquinoline-3-carbonitrile (Example 72a) (0.95 g, 4.26 mmol) and ammonium acetate (0.36 g, 4.67 mmol) were heated in acetic acid (20 mL) at 140 C. for 4 hours, then cooled to room temperature. The reaction was poured into ice water (400 mL), and the resultant precipitate was collected by filtration to give 4-chloro-2-oxo-1,2-dihydroquinoline-3-carbonitrile (0.668 g, 77%) as a light yellow solid. M.p.: >250 C. 1H NMR (400 MHz, DMSO-d6) delta 7.42 (m, 2H), 7.79 (m, 1H), 7.96 (d, J=8.4 Hz, 1H), 12.72 (s, 1H). MS 205 (MH-).
With water; trifluoroacetic acid; at 100℃; for 1h; 4-chloro-2-oxo-L2-dihvdroquinoline-3-carbonitrile (1-5) In a round-bottomed flask, 2,4-dichloroquinoline-3-carbonitrile (1-4) (15g, 67.2mmol), was dissolved in 40 ml of a 4: 1 mixture of TFA and H20. The reaction mixture was heated to 100 C for 1 hour, then allowed to cool and poured into methanol. The precipitate was filtered off and dried to give 4-chloro-2-oxo-l,2-dihydroquinoline-3-carbonitrile (1-4) HRMS (M+H)+: observed = 205.1, calculated = 205.6
With trifluoroacetic acid; In water; at 100℃; for 1h; In a round-bottomed flask, 2,4-dichloroquinoline-3-carbonitrile (1-4) (15g, 67.2mmol), was dissolved in 40 ml of a 4: 1 mixture of TFA and H20. The reaction mixture was heated to 100 C for 1 hour, then allowed to cool and poured into methanol. The precipitate was filtered off and dried to give 4-chloro-2-oxo-l,2-dihydroquinoline-3-carbonitrile (1-4) HRMS (M+H)+: observed = 205.1, calculated = 205.6
With trifluoroacetic acid; In water; at 100℃; for 1h; In a round-bottomed flask, 2,4-dichloroquinoline-3 -carbonitrile (1-4) (1 5g,67.2mmol), was dissolved in 40 ml of a 4:1 mixture of TFA and H20. The reaction mixture was heated to 100C for 1 hour, then allowed to cool and poured into methanol. The precipitate was filtered off and dried to give 4-chloro-2-oxo- 1 ,2-dihydroquinoline-3 -carbonitrile (1-4) HRMS(M+H): observed = 205.1, calculated = 205.6

YieldReaction ConditionsOperation in experiment
In the same manner as shown in Reference Example 24, the target compound was obtained. 1H-NMR (DMSO-d6, 300 MHz): delta 7.37-7.43 (2H, m), 7.75-7.81 (1H, m), 7.94-7.97 (1H, m), 12.70 (1H, br s). LC/MS (ESI): m/z 205.1 (M+1).
  • 4
  • [ 680210-85-9 ]
  • [ 71993-20-9 ]
YieldReaction ConditionsOperation in experiment
25% <strong>[680210-85-9]4-chloro-2-oxo-1,2-dihydroquinoline-3-carbonitrile</strong> (example 72) (0.66 g, 3.23 mmol) was suspended in DMF (7 mL), and 4-methoxybenzylamine (0.94 mL, 7.26 mmol) was added. The reaction was heated at 100 C. for 1 hour and the DMF was removed under vacuum. The residue was dissolved in TFA (6 mL) and stirred at room temperature for 30 minutes and dichloromethane (10 mL) was added. The solid product that formed was collected, suspended in water and the solution stirred overnight. The solid was collected by filtration to give 4-amino-2-oxo-1,2-dihydroquinoline-3-carbonitrile (0.150 g, 25%) as a white solid. M.p.: >250 C. 1H NMR (400 MHz, DMSO-d6) delta 7.19 (m, 2H), 7.57 (m, 1H), 7.88 (bs, 2H), 8.12 (d, J=7.6 Hz, 1H), 11.23 (s, 1H). MS 186 (MH+).
  • 6
  • [ 680210-85-9 ]
  • [ 98-80-6 ]
  • [ 16560-18-2 ]
YieldReaction ConditionsOperation in experiment
With bis(tri-t-butylphosphine)palladium(0); caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 0.166667h;Microwave irradiation; Inert atmosphere; Sealed tube; 4-phenyl-2-oxo-L2-dihydroquinoline-3-carbonitrile (1-7) To a microwave vial, 4-chloro-2-oxo-l,2-dihydroquinoline-3-carbonitrile (1-5, lg, 4.89 mmol) was added along with phenylboronic acid 1-6 (969 mg, 9.77 mmol), cesium carbonate (1.263g, 9.77 mmol), and DMF (3 mL). The reaction was degassed, then bis(tri-t- butylphosphine)palladium(O) (51 mg, 0.1 mmol) was added. The sealed reaction vessel was heated under microwave irradiation for 10 min at 100 C. The reaction mixture was partitioned between AcOEt (3x75 ml) and saturated aqueous NaHC03 (80 ml). The combined organic layers were dried over MgS04 and concentrated. The yellow solid was then redissolved in AcOEt and recrystalized to give 4-phenyl-2-oxo-l,2-dihydroquinoline-3-carbonitrile (1-7). MR (500 MHz, DMSO-d6): delta 12.6 (s, 1 H); 7.71 (m, 1 H); 7.62 (m, 3 H); 7.53 (m, 2 H); 7.45 (m, 1 H); 7.21 (m, 2 H). MS (M+H)+: observed = 247.2, calculated = 247.3.
  • 7
  • [ 15000-43-8 ]
  • [ 680210-85-9 ]
  • 8
  • [ 15000-43-8 ]
  • [ 680210-85-9 ]
  • 9
  • [ 680210-85-9 ]
  • [ 108-93-0 ]
  • 4-cyclohexyloxy-2-oxo-1,2-dihydroquinoline-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a microwave flask charged with DMF (0.3 ml), cyclohexanol (50 mg, 0.499 mmol) was added, followed by NaH (20 mg 60% dispersion in mineral oil, 0.499 mmol), portionwise. The reaction mixture was stirred at r.t. for 1 hour then 4-chloro-2-oxo-l,2- dihydroquinoline-3-carbonitrile (1-4, 51. lmg, 0.250 mmol) was added. The reaction was heated to 110 C under microwave irradiation for 10 min, cooled, the solvent removed and the crude residue was purified via reverse phase to give 4-(cyclohexyloxy)-2-oxo-l,2-dihydroquinoline-3-carbonitrile (1-7). NMR (500 MHz, DMSO-d6): delta 12.1 (s, 1 H); 7.91 (m, 1 H); 7.68 (m, 1 H); 7.35-7.23 (m, 2 H); 5.22 (m, 1 H); 2.09 (m, 2 H); 1.80-1.69 (m, 4 H); 1.59-1.25 (m, 4 H). HRMS (M+H)+: observed = 268.31, calculated = 268.31.
  • 10
  • [ 680210-85-9 ]
  • 1-pyrrolidine-3-yl-1H-pyrazole hydrochloride [ No CAS ]
  • (R)-4-(3-[1H-pyrazol-1-yl]pyrrolidin-1-yl)-2-oxo-1,2-dihydroquinoline-3-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 100℃; for 0.5h; 4-Chloro-2-oxo-1,2-dihydroquinoline-3-carbonitrile (1-5) (20g, 98 mmol), 1-pyrrolidine-3-yl-1H-pyrazole hydrochloride (23.8 g, 137 mmol), DIPEA (68.3 mL, 391 mmol), andDMF (244 mL) were heated to 100 C for thirty minutes. The reaction was cooled and partitionedbetween water and EtOAc, and the aqueous layer was extracted with EtOAc (x3). The combined organic layers were concentrated, and the residue slurried in water to result in a brown solid which was collected by filtration. The mother liquor was aged overnight and the resulting additionalbrown material was collected by filtration. The combined solids were purified by SCF method(55% C02, 45% MeOH, IA column with 0.1% DEA additive), and the second peak (6.55 mm.)collected to give the single enantiomer (R)-4-(3 -[ 1H-pyrazol- 1 -yl]pyrrolidin- 1 -yl)-2-oxo- 1,2-dihydroquinoline-3-carbonitrile (1-7) as a beige solid (9.1 g, 3 1%). ?HNIVIR (500 MHz, CD3OD):8.09 (m, 1 H); 7.78 (m, 1 H); 7.5 1-7.59 (m, 2 H); 7.25 (m, 1 H); 7.19 (m, 1 H); 6.33 (m, 1 H);5.18 (m, 1 H); 4.58 (m, 1 H); 4.44 (m, 1 H); 4.40 (m, 1 H); 4.29 (m, 1 H); 2.53 (m, 2 H). MS(M+H): observed = 306.08, calculated = 306.334
 

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