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Chemical Structure| 22246-02-2 Chemical Structure| 22246-02-2

Structure of 22246-02-2

Chemical Structure| 22246-02-2

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Product Details of [ 22246-02-2 ]

CAS No. :22246-02-2
Formula : C9H8ClNO
M.W : 181.62
SMILES Code : O=C1NCCC2=C1C=CC(Cl)=C2
MDL No. :MFCD04114866
InChI Key :RQKCSUSXBKSENU-UHFFFAOYSA-N
Pubchem ID :19375637

Safety of [ 22246-02-2 ]

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

Computational Chemistry of [ 22246-02-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 51.22
TPSA ?

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

29.1 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.78
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

1.86
Log Po/w (WLOGP)?

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

1.25
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.

2.02
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

2.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.93

Water Solubility

Log S (ESOL):?

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

-2.51
Solubility 0.564 mg/ml ; 0.00311 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.

-2.09
Solubility 1.47 mg/ml ; 0.00808 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

-3.78
Solubility 0.0299 mg/ml ; 0.000165 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.

-6.09 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)

1.43

Application In Synthesis of [ 22246-02-2 ]

* 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 [ 22246-02-2 ]

[ 22246-02-2 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 22246-02-2 ]
  • [ 118650-08-1 ]
  • [ 1440520-17-1 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; (S,S)-1,2-diaminocyclohexane; caesium carbonate; In 1,4-dioxane; at 150℃; for 2h;Inert atmosphere; (5-Bromo-pyridin-3-yl)-acetic acid methyl ester (230 mg, 1.0 mmol), 6-chloro-3,4- dihydro-2H-isoquinolin-l-one (intermediate A-2) (182 mg, 1.0 mmol), Cul (40 mg, 0.21 mmol), Cs2C03 (650 mg, 2.0 mmol) and (+)-(lS,lS)-l,2-diaminocyclohexane (0.1 mL, 0.8 mmol) were dissolved in dioxane (4.0 ml) and the resulting reaction mixture was heated at 150 C for 2 hours before it was poured into H20 (20 mL) and extracted with EtOAc (2 x 100 mL). The combined organic layer was washed with brine, dried over anhy. Na2S04, filtered and concentrated in vacuo to give a crude product (230 mg, 72.5%) as light brown oil. MS: 317.1 (M+H+)
With copper(l) iodide; (S,S)-1,2-diaminocyclohexane; caesium carbonate; In 1,4-dioxane; at 150℃; for 2h; [B] [5-(6-Chloro-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-pyridin-3-yl]-acetic acid (5-Bromo-pyridin-3-yl)-acetic acid methyl ester (230 mg, 1.0 mmol), 6-chloro-3,4-dihydro-2H-isoquinolin-1-one (intermediate A-2) (182 mg, 1.0 mmol), CuI (40 mg, 0.21 mmol), Cs2CO3 (650 mg, 2.0 mmol) and (+)-(1S,1S)-1,2-diaminocyclohexane (0.1 mL, 0.8 mmol) were dissolved in dioxane (4.0 ml) and the resulting reaction mixture was heated at 150 C. for 2 hours before it was poured into H2O (20 mL) and extracted with EtOAc (2*100 mL). The combined organic layer was washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product (230 mg, 72.5%) as light brown oil. MS: 317.1 (M+H+).
  • 2
  • [ 53710-18-2 ]
  • [ 22246-02-2 ]
  • 6-chloro-2-(5-iodo-3-pyridyl)-3,4-dihydroisoquinolin-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With potassium phosphate; (S,S)-1,2-diaminocyclohexane; In 1,4-dioxane; for 3h;Reflux; Inert atmosphere; GammaAlpha1 6-Chloro-2-(5-iodo-3-pyridyl)-3,4-dihvdroisoquinolin-l-one A mixture of 6-chloro-3,4-dihydro-2H-isoquinolin-l-one (intermediate A-1, 380 mg, 2 mmol), <strong>[53710-18-2]3,5-diiodopyridine</strong> (1.192 g, 3.6 mmol), Cul (152 mg, 0.8 mmol), (IS, 2S)- cyclohexane-l,2-diamine (182.4 mg, 1.6 mmol) and K3PO4 (848 mg, 4 mmol) in dioxane (5 mL) was heated to reflux temperature for 3 hours. After cooling to room temperature, the mixture was poured into satd. aq. NaHC03 solution (20 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine, dried over anhy. Na2S04, filtered and concentrated in vacuo to give a crude product, which was then purified by silica gel flash chromatography to afford the title compound (350 mg, 46%) as a white solid. MS: 385.1 (M+H+).
  • 3
  • [ 22246-02-2 ]
  • [ 33537-99-4 ]
YieldReaction ConditionsOperation in experiment
With dimethylsulfide borane complex; In tetrahydrofuran;Reflux; To a solution of 6-chloro-3,4-dihydroisoquinolin-1 (2/-/)-one (33 g, 182 mmol) in THF (330 ml.) was added dropwise BH3-Me2S (73 ml_, 729 mmol). The reaction mixture was refluxed overnight. The mixture was cooled to ambient temperature and then quenched with 6L/ aqueous HCI (300 mL). THF was removed under reduced pressure and the remaining solution was refluxed overnight. The mixture was concentrated to a certain volume and then basified with 2N aqueous NaOH. The resulting mixture was extracted with DCM. The DCM layer was dried over anhydrous sodium sulfate and concentrated to provide 6-chloro-1 ,2,3,4- tetrahydroisoquinoline.
 

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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