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Chemical Structure| 40365-61-5 Chemical Structure| 40365-61-5

Structure of 40365-61-5

Chemical Structure| 40365-61-5

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Product Details of [ 40365-61-5 ]

CAS No. :40365-61-5
Formula : C9H14O2
M.W : 154.21
SMILES Code : C#CCCOC1CCCCO1
MDL No. :MFCD00012352
InChI Key :ZQZSNKJFOFAJQX-UHFFFAOYSA-N
Pubchem ID :142440

Safety of [ 40365-61-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 40365-61-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 0
Fraction Csp3 0.78
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 43.59
TPSA ?

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

18.46 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.59
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

1.52
Log Po/w (WLOGP)?

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

1.63
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.

1.48
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

2.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.88

Water Solubility

Log S (ESOL):?

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

-1.56
Solubility 4.29 mg/ml ; 0.0278 mol/l
Class?

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

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.52
Solubility 4.7 mg/ml ; 0.0305 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

-1.4
Solubility 6.21 mg/ml ; 0.0403 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.

-6.16 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)

3.63

Application In Synthesis of [ 40365-61-5 ]

* 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 [ 40365-61-5 ]

[ 40365-61-5 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 40365-61-5 ]
  • [ 211029-67-3 ]
  • {3-[4-(Tetrahydro-pyran-2-yloxy)-but-1-ynyl]-pyridin-4-yl}-carbamic acid tert-butyl ester [ No CAS ]
  • 2
  • [ 40365-61-5 ]
  • [ 412947-54-7 ]
  • [ 1253733-56-0 ]
YieldReaction ConditionsOperation in experiment
78% With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 75℃;Inert atmosphere; Example 58. Preparation of 2-[2-(2-hydroxyethyl)-1H-indol-6-yl]-5,7-dimethoxy-3H-quinazolin-4-one [0335] To a degassed solution of <strong>[412947-54-7]methyl-3-amino-4-iodobenzoate</strong> (2.00 g, 7.22 mmol) in a mixture of 5:1 DMF-triethylamine (30 ml_) were added PdCI2(PPh3)2 (0.25 g, 0.36 mmol) and copper (I) iodide (0.41 g, 2.16 mmol) and the mixture was degassed again. A degassed solution of 2-(3-butynyloxy)tetrahydro-2H-pyran (1.7 ml_, 10.83 mmol) in a mixture of 5:1 DMF-triethylamine (12 ml_) was added drop-wise at 75C over a period of 45 minutes under nitrogen. Soon after the addition, TLC showed completion of the reaction. The reaction mixture was cooled to room temperature, solvent was removed under reduced pressure, and the residue was diluted with water (75 mL) and extracted with ethyl acetate (3 * 50 mL). The organic phase was washed with water (50 mL), brine (50 mL), and dried over anhydrous MgSO4. The solvent was evaporated and the crude product was purified by column chromatography (silica gel 230-400 mesh; 2:1 hexanes and ethyl acetate as eluent) to obtain 3-amino-4- [4-(tetrahydropyran-2-yloxy)-but-1-ynyl]benzoic acid methyl ester as a brown solid. Yield: 1.7O g (78%).[0336] To a stirred solution of 3-amino-4-[4-(tetrahydropyran-2-yloxy)-but-1-ynyl]benzoic acid methyl ester (1.68 g, 5.55 mmol) in anhydrous pyridine (5 mL) was added acetyl chloride (0.43 mL, 6.11 mmol) at 00C under nitrogen. Stirring was continued at 00C. After 30 minutes TLC showed completion of the reaction. Pyridine was removed under reduced pressure and the residue was diluted with ethyl acetate (100 ml_). The resulting mixture was washed with aq 2 N HCI (20 ml_), water (2 x 15 ml_) and brine (20 mL). After drying over anhydrous MgSO4, solvent was removed to obtain 3-acetylamino-4-[4-(tetrahydropyran-2-yloxy)-but-1-ynyl]benzoic acid methyl ester as a beige solid. Yield: 1.67 g (87%). Crude product was used in the next step without further purification.[0337] A 1.0 M solution of tetrabutylammonium fluoride (9.67 mL, 9.67 mmol) in THF was added to a solution of 3-acetylamino-4-[4- (tetrahydropyran-2-yloxy)-but-1-ynyl]benzoic acid methyl ester (1.67 g, 4.83 mmol) in anhydrous THF (20 mL) at room temperature. The resulting reddish-brown solution was heated at reflux for 2 hours and then allowed to cool to room temperature. The solvent was removed under reduced pressure and the residue was taken in water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The organic phase was washed with water (25 mL), brine (50 mL), and dried over anhydrous MgSO4. The solvent was evaporated and the crude product was purified by column chromatography on (silica gel 230-400 mesh; dichloromethane as eluent) to give 2-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indole-6-carboxylic acid methyl ester as a light brown solid. Yield: 1.27 g (87%). [0338] To a suspension of lithium aluminum hydride (0.32 g, 8.37 mmol) in anhydrous THF (20 mL) was added a solution of 2-[2-(tetrahydropyran-2- yloxy)ethyl]-1H-indole-6-carboxylic acid methyl ester (1.27 g, 4.19 mmol) in anhydrous THF (10 mL) at -30C to -200C dropwise over a period of 15 minutes under nitrogen. The temperature was allowed to warm to room temperature and stirring continued for 15 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution at 00C, diluted with ethyl acetate (50 mL), and filtered. The solid was washed with ethyl acetate. The combined organic phase was dried over anhydrous MgSO4. The solvent was evaporated and the crude product was purified by the Simpliflash system (3:2 ethyl acetate-hexanes as eluent) to give {2-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indol-6-yl}-methanol as a white solid. Yield: 0.61 g (53%).[0339] IBX (0.62 g, 2.21 mmol) was added to a solution of {2-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indol-6-yl}-methanol (0.61 g, 2.21 mmol) in DMSO (10 ml_). After 30 min, the reaction mixture became a clear solution. Stirring was continued at room temperature for 2 hours and during this time, some solid precipitated. Water (50 mL) was added, the solid was filtered, and washed with ethyl acetate (50 mL). The filtrate was collected and extracted with ethyl acetate (3 * 20 mL). The organic phase was washed with brine (30 mL) and dried over anhydrous MgSO4. Removal of solvent gave 2-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indole-6-carbaldehyde as a light brown solid. Yield: 0.60 g (99%).[0340] To a solution of 2-amino-4,6-dimethoxy-benzamide (0.48 g, 2.42 mmol) and 2-[2-(tetrahydropyran-2-yloxy)ethyl]-1H-indole-6-carbaldehyde (0.60 g, 2.20 mmol) in N,N-dimethylacetamide (20 mL) were added NaHSO3 (58.5 wt%, 0.60 g, 3.30 mmol) and p-toluenesulfonic acid monohydrate (0.17 g, 0.88 mmol). The reaction mixture was heated at 1100C for 20 hours and then cooled to room temperature. N,N-dimethylacetamide was removed under reduced pressure. The residue was diluted with saturated sodium carbonate solution (50 mL) and extracted with dichloromethane (4 x 25 mL). The combined organic phase...
78% With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In N,N-dimethyl-formamide; at 75℃; for 0.75h;Inert atmosphere; To a degassed solution of <strong>[412947-54-7]methyl-3-amino-4-iodobenzoate</strong> (2.00 g, 7.22 mmol) in a mixture of 5:1 DMF-triethylamine (30 mL) were added PdCl2(PPh3)2 (0.25 g, 0.36 mmol) and copper (I) iodide (0.41 g, 2.16 mmol) and the mixture was degassed again. A degassed solution of 2-(3-butynyloxy)tetrahydro-2H-pyran (1.7 mL, 10.83 mmol) in a mixture of 5:1 DMF-triethylamine (12 mL) was added drop-wise at 75 C. over a period of 45 minutes under nitrogen. Soon after the addition, TLC showed completion of the reaction. The reaction mixture was cooled to room temperature, solvent was removed under reduced pressure, and the residue was diluted with water (75 mL) and extracted with ethyl acetate (3*50 mL). The organic phase was washed with water (50 mL), brine (50 mL), and dried over anhydrous MgSO4. The solvent was evaporated and the crude product was purified by column chromatography (silica gel 230-400 mesh; 2:1 hexanes and ethyl acetate as eluent) to obtain 3-amino-4-[4-(tetrahydropyran-2-yloxy)-but-1-ynyl]benzoic acid methyl ester as a brown solid. Yield: 1.70 g (78%)
 

Historical Records

Technical Information

Categories

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