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Structure of 1082041-78-8

Chemical Structure| 1082041-78-8

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Product Details of [ 1082041-78-8 ]

CAS No. :1082041-78-8
Formula : C10H11NO
M.W : 161.20
SMILES Code : O=C1NCCC2=C1C=CC(C)=C2
MDL No. :MFCD09838960
InChI Key :UYZJTSNVWCNCIR-UHFFFAOYSA-N
Pubchem ID :22890891

Safety of [ 1082041-78-8 ]

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

Computational Chemistry of [ 1082041-78-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.3
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 51.17
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.

1.81
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

1.6
Log Po/w (WLOGP)?

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

0.9
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.

1.76
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

2.57
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.73

Water Solubility

Log S (ESOL):?

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

-2.22
Solubility 0.977 mg/ml ; 0.00606 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.

-1.82
Solubility 2.43 mg/ml ; 0.015 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

-3.54
Solubility 0.0461 mg/ml ; 0.000286 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.

-6.15 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)

1.4

Application In Synthesis of [ 1082041-78-8 ]

* 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.

  • Upstream synthesis route of [ 1082041-78-8 ]

[ 1082041-78-8 ] Synthesis Path-Upstream   1~11

  • 1
  • [ 147497-32-3 ]
  • [ 13061-96-6 ]
  • [ 1082041-78-8 ]
YieldReaction ConditionsOperation in experiment
95.2% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,4-dioxane; water at 105℃; for 16 h; Inert atmosphere To a mixture of 6-bromo-3,4-dihydro-2H-isoquinolin-1-one (19.0 g, 82.4 mmol),CH3B(OH)2 (20.8 g, 329 mmol) and Na2CO3 (18.4 g, 165 mmol) in 1,4-dioxane (200 mL)and water (10.0 mL) is added [1,1’-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (2.46 g, 3.29 mmol) under a nitrogen atmosphere and the mixture is stirred at 105 °C for 16 hours under a nitrogen atmosphere. The suspension is filtered through a pad of diatomaceous earth and the filter cake is washed with DCM (3 x250 mL). The combined filtrates are washed with water (100 mL) and brine (80 mL), dried over Na2SO4, and the solvent isevaporated under reduced pressure. The crude product is purified by silica gel flash chromatography, eluting with a gradient of 0percent to 50percent EtOAc in PE to give the title compound (13.0 g, 95.2percent) as a yellow solid. ES/MS (m/z): 162.0 (M+H), ‘H NIVIR (400MHz, CDC13) 7.94 (d, J=8.0 Hz, 1H), 7.15 (d, J=7.8 Hz, 1H), 7.02 (s, 1H), 6.89 (br s, 1H),3.55 (dt, J=2.9, 6.6 Hz, 2H), 2.94 (t, J=6.5 Hz, 2H), 2.37 (s, 3H).
References: [1] Patent: WO2018/160406, 2018, A1, . Location in patent: Page/Page column 10; 11.
  • 2
  • [ 1216990-26-9 ]
  • [ 1082041-78-8 ]
YieldReaction ConditionsOperation in experiment
19% at 110℃; for 1 h; Preparation of Intermediate 6-methyl-3,4-dihydroisoquinolin-1(2H)-one (I-69d)
Ethyl 3-methylphenethylcarbamate (I-69c: 13.5 g, 65.217 mmol) was reacted with P2O5 (18.51 g, 130.434 mmol) and POCl3 (135 mL) at 110° C. for 1 hour.
The reaction mass was concentrated under reduced pressure, quenched with ice, basified using saturated NaHCO3 solution and extracted using ethyl acetate.
The organic layer was washed with brine solution, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product.
Purification by column chromatography on silica gel (1percent methanol in DCM) afforded 2 g of the product (19percent yield). LCMS: 75.24percent, m/z 162.3 (M+1)
References: [1] Patent: US2014/45872, 2014, A1, . Location in patent: Paragraph 1035.
[2] Patent: WO2012/35078, 2012, A1, . Location in patent: Page/Page column 168.
  • 3
  • [ 1216826-48-0 ]
  • [ 1082041-78-8 ]
YieldReaction ConditionsOperation in experiment
32% at 145℃; for 0.166667 h; To the compound 21a (2.5 g, 12.9 mmol) was added poly-phosphoric acid (30 g). The reaction mixture was heated at 145 °C for 10 min and cooled down at 0 °C. Water was added and the organic phase was extracted with CH2Cl2. The combinded organic fractions were dried over Na2SO4 and the solvent was evaporated in vacuo. The resulting residue was purified by a column chromatography (EtOAc:hexane = 1:1) to give compound 23a (674 mg, 32percent) as an ivory crystal. 1H NMR (300 MHz, CDCl3) : 7.95 (d, J = 7.8 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 7.02 (s, 1H), 6.41 (bs, 1H), 3.55 (td, J = 6.6, 2.7 Hz, 2H), 2.95 (t, J = 6.6 Hz 2H), 2.38 (s, 3H).
References: [1] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 789 - 801.
  • 4
  • [ 4593-38-8 ]
  • [ 1082041-78-8 ]
References: [1] ACS Medicinal Chemistry Letters, 2019, vol. 10, # 1, p. 74 - 79.
  • 5
  • [ 620-23-5 ]
  • [ 1082041-78-8 ]
References: [1] Patent: WO2012/35078, 2012, A1, .
[2] Patent: US2014/45872, 2014, A1, .
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 789 - 801.
  • 6
  • [ 55755-17-4 ]
  • [ 1082041-78-8 ]
References: [1] Patent: WO2012/35078, 2012, A1, .
[2] Patent: US2014/45872, 2014, A1, .
[3] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 789 - 801.
  • 7
  • [ 55755-17-4 ]
  • [ 1082041-78-8 ]
  • [ 1082041-79-9 ]
References: [1] Journal of Organic Chemistry, 2012, vol. 77, # 20, p. 9313 - 9328,16.
  • 8
  • [ 22568-43-0 ]
  • [ 1082041-78-8 ]
References: [1] Patent: WO2012/35078, 2012, A1, .
[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 789 - 801.
  • 9
  • [ 1216826-48-0 ]
  • [ 1082041-78-8 ]
  • [ 1082041-79-9 ]
References: [1] Journal of Organic Chemistry, 2012, vol. 77, # 20, p. 9313 - 9328,16.
  • 10
  • [ 22568-43-0 ]
  • [ 1082041-78-8 ]
References: [1] Patent: US2014/45872, 2014, A1, .
  • 11
  • [ 34598-49-7 ]
  • [ 1082041-78-8 ]
References: [1] Patent: WO2018/160406, 2018, A1, .
 

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