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Chemical Structure| 1011-65-0 Chemical Structure| 1011-65-0

Structure of 1011-65-0

Chemical Structure| 1011-65-0

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Product Details of [ 1011-65-0 ]

CAS No. :1011-65-0
Formula : C10H9NO2
M.W : 175.18
SMILES Code : COC(=O)C1=CC2=C(NC=C2)C=C1
MDL No. :MFCD00153023
InChI Key :DRYBMFJLYYEOBZ-UHFFFAOYSA-N
Pubchem ID :2737635

Safety of [ 1011-65-0 ]

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

Computational Chemistry of [ 1011-65-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 9
Fraction Csp3 0.1
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 49.58
TPSA ?

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

42.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.84
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

1.23
Log Po/w (WLOGP)?

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

1.95
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.

1.38
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

2.36
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.75

Water Solubility

Log S (ESOL):?

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

-2.08
Solubility 1.45 mg/ml ; 0.00829 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.

-1.71
Solubility 3.4 mg/ml ; 0.0194 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

-3.36
Solubility 0.0772 mg/ml ; 0.000441 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.

-6.5 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)

1.26

Application In Synthesis of [ 1011-65-0 ]

* 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 [ 1011-65-0 ]

[ 1011-65-0 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 1011-65-0 ]
  • [ 74-88-4 ]
  • [ 128742-76-7 ]
YieldReaction ConditionsOperation in experiment
97% Preparation of 1-Methyl-5- [5- (2-phenoxy-ethylsulfanylmethyl)- [1, 3,4] oxadiazol-2-yl]- 1H-indole a) 1-Methyl-lH-indole-5-carboxylic acid methyl ester A DMF solution of methyl indole-5-carboxylate (5.0 g, 28.54 mmol, 1 eq. ) was cooled in an ice bath and then treated with sodium hydride (1.37 g, 34.29 mmol, 1.2 eq. ). After 20 minutes at 0C, the reaction was treated with iodomethane (6.08 g, 2.7 mL, 42. 81 mmol, 1.5 eq. ). After stirring for 4 hours, the reaction was quenched with water. The reaction was extracted twice with 150 mL of ethyl acetate and the organic layers were combined, dried, filtered, and the solvent removed in vacuo leaving a yellow oil that was triturated with hexane to obtain 1-methyl-lH-indole-5-carboxylic acid methyl ester (5.22 g, 97% yield) as a tan solid.
76% Preparation of methyl 1-methyl-1 f-indoie-5-cari30xylate To a suspension of aH (264 mg, 1.1 mmoi) in DMF (20 ml) was added methyl 1H-indoie-5-carboxylate (1.05 g, 6 mmoi) at 0 QC and the resulting mixture was stirred for 20 minutes, Mel (1.70 g, 2,2 mmo) was added to the reaction mixture, which was then allowed to warm to 50 C overnight. The reaction liquid was partitioned between EtOAc and water. The organic layer was washed with water and brine, dried over Na2S04 and concentrated to give the crude product, which was purified by silica gel column (EtQAc/petroleum ether - 1/10) to give the target compound (860 mg, 76%). LCMS: m/z 190.1 [M+Hf,
56% With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 8h; 1H-indole-6-carboxylic acid methyl ester (1.0g, 5.71mmol) was dissolved in dimethylformamide (10ml), and methyl iodide (0.53ml, 8.56mmol) and sodium hydride (374mg, 8.56mmol) were added dropwise thereto at 0. The mixture was stirred for 8 hours at room temperature. 1N hydrochloric acid solution was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and filtered. Filtrate was distilled under reduced pressure and separated by column chromatography to obtain the title compound (600mg, 56%).
Sodium hydride (1.71 g, 42.80 mmol, 60% in mineral oil) was added at 0 C. in portions to a stirred solution of methyl indole-5-carboxylate (5.0 g, 28.53 mmol, CASRN 1670-81-1) in DMF over a 30 min period. While still at 0 C. MeI (5.33 mL, 85.61 mmol) was added. The resulting mixture was stirred at 0 C. for 60 min then at RT overnight. The mixture was partitioned between H2O and EtOAc and the aqueous layer was further extracted with EtOAc. The combined organic extracts were washed with water, dried (MgSO4), filtered and concentrated to afford 4.91 g of 1-methyl-1H-indole-5-carboxylic acid methyl ester (53).
With potassium hydride; In tetrahydrofuran; at 20℃; for 0.5h; Step A. 1-Methyl-indole-5-carboxylic acid methyl ester. Under an atmosphere of nitrogen, a solution of indole-5-carboxylic acid methyl ester (2.5 g, 14.3 mmol) in dry tetrahydrofuran (20 mL) was added dropwise to a stirred slurry of hexane-washed potassium hydride (1.63 g, 14.3 mmol, 35% in oil). When the hydrogen evolution ceased, iodomethane (1.3 mL, 21.5 mmol) was added to the stirred solution. After an additional 30 minutes at room temperature, the precipitate was filtered and washed with diethyl ether. The filtrate was concentrated in vacuo and the residue triturated with hexane to provide the title compound as a yellow solid (2.6 g).
With sodium hydride; In dimethyl sulfoxide; at 0℃; for 2h; TE4O was synthesized by the reaction scheme:Methyl 1-methyl-1H-indole-5-carboxylate was prepared according to the article, Org. Lett. 2014, 16, 1124-1127, which is hereby incorporated by reference in its entirety. Rf = 0.49 in hexanes: EtOAc = 2:1. ?HNIVIR (400 MHz, CDC13) ppm 8.4 (s, 1H) 7.9 (d, J 8.6 Hz, 1H) 7.3 (d, J= 9.4 Hz, 1H) 7.1 (d, J= 3.1 Hz, 1H) 6.6 (d, J= 3.9 Hz, 1H) 3.9 (s, 3H)3.8 (s, 3H). ?3C NMR (101 IVIHz, CDC13) ppm 168.2, 139.0, 130.2, 127.9, 123.9, 122.8,121.3, 108.8, 102.6, 51.7, 32.9.

  • 2
  • hexane-washed potassium hydride [ No CAS ]
  • [ 1011-65-0 ]
  • [ 74-88-4 ]
  • [ 128742-76-7 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; Step A. 1-Methyl-indole-5-carboxylic Acid Methyl Ester Under an atmosphere of nitrogen, a solution of indole-5-carboxylic acid methyl ester (2.5 g, 14.3 mmol) in dry tetrahydrofuran (20 mL) was added dropwise to a stirred slurry of hexane-washed potassium hydride (1.63 g, 14.3 mmol, 35% in oil). When the hydrogen evolution ceased, iodomethane (1.3 mL, 21.5 mmol) was added to the stirred solution. After an additional 30 minutes at room temperature, the precipitate was filtered and washed with diethyl ether. The filtrate was concentrated in vacuo and the residue triturated with hexane to provide the title compound as a yellow solid (2.6 g). NMR (CDCl3, 400 MHz): delta 3.82 (s, 3H), 3.93 (s, 3H), 6.58 (dd, 1H), 7.10 (d, 1H), 7.32 (d, 1H), 7.92 (dd, 1H), 8.39 (s, 1H); MS (El, m/z): 189 [M]+, 158, 130.
In tetrahydrofuran; Step A. 1-Methyl-indole-5-carboxylic acid methyl ester Under an atmosphere of nitrogen, a solution of indole-5-carboxylic acid methyl ester (2.5 g, 14.3 mmol) in dry tetrahydrofuran (20 mL) was added dropwise to a stirred slurry of hexane-washed potassium hydride (1.63 g, 14.3 mmol, 35% in oil). When the hydrogen evolution ceased, iodomethane (1.3 mL, 21.5 mmol) was added to the stirred solution. After an additional 30 minutes at room temperature, the precipitate was filtered and washed with diethyl ether. The filtrate was concentrated in vacuo and the residue triturated with hexane to provide the title compound as a yellow solid (2.6 g). NMR (CDCl3, 400 MHz): delta 3.82 (s, 3H), 3.93 (s, 3H), 6.58 (dd, 1H), 7.10 (d, 1H), 7.32 (d, 1H), 7.92 (dd, 1H), 8.39 (s, 1H) MS (EI, m/z): 189 [M]+, 158, 130
  • 3
  • [ 1480-65-5 ]
  • [ 1011-65-0 ]
  • [ 1252779-91-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 200℃; for 2h;Microwave irradiaition; A mixture of Ij (1.14 mmol, 200 mg), laa (1.14 mmol, 150 mg), K2CO3 (2.28 mmol, 315 mg) and NMP (1.5 mL) was heated at 200 0C in a microwave reactor for 2 h. The mixture was poured into water (50 mL) and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under vacuo. Purification was carried by flash column chromatography (silica gel, 15percent EtO Ac/heptane) to give 290 mg of lbb (290 mg).
  • 4
  • [ 1011-65-0 ]
  • [ 119999-22-3 ]
  • [ 1423410-73-4 ]
  • 5
  • [ 1011-65-0 ]
  • [ 119999-22-3 ]
  • [ 1423410-83-6 ]
  • 6
  • [ 29006-02-8 ]
  • [ 1011-65-0 ]
  • methyl 3-(4-methoxybutanoyl)indole-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% To a solution of oxalyl chloride (2.08 g, 16.4 mmol) in dry toluene (10 mL) was added dropwise at 0 C a solution of <strong>[29006-02-8]4-methoxybutyric acid</strong> (1.76 g, 14.9 mmol) in dry toluene (10 mL). After stirring the mixture at room temperature over night, the solvent was distilled off. The residue was dissolved in dry CH2Cl2 (30 mL) and treated with methyl indole-5-carboxylate (801 mg, 4.57 mmol) at room temperature. Then AlCl3 (1.72 g, 12.9 mmol) was added at 0 C and the mixture was stirred at this temperature for 15 min. After addition of water, the reaction mixture was exhaustively extracted with ethyl acetate. The combined organic layers were dried (Na2SO4) and concentrated. Recrystallization from ethyl acetate gave the pure product (588 mg, 47%). C15H17NO4 (275.3); mp 167-168 C; 1H NMR (DMSO-d6): delta (ppm) 1.83-1.90 (m, 2H), 2.90 (t, 2H, J = 7.3 Hz), 3.21 (s, 3H), 3.37 (t, 2H, J = 6.5 Hz), 3.85 (s, 3H), 7.53 (d, 1H, J = 8.6 Hz), 7.82 (dd, 1H, J = 8.6 Hz and 1.7 Hz), 8.44 (s, 1H), 8.87-8.88 (m, 1H), 12.22 (sbroad, 1H); MS (EI): m/z (%) 275 (4) [M]+, 217 (100).
  • 7
  • [ 1593-60-8 ]
  • [ 1011-65-0 ]
  • [ 1627964-15-1 ]
  • 8
  • [ 1011-65-0 ]
  • methyl halide [ No CAS ]
  • [ 128742-76-7 ]
  • 9
  • [ 1011-65-0 ]
  • [ 105-45-3 ]
  • [ 621-63-6 ]
  • methyl 3-(4-(methoxycarbonyl)-5-methyl-2,3-dihydrofuran-3-yl)-1H-indole-5-carboxylate [ No CAS ]
  • 10
  • [ 2150-46-1 ]
  • [ 1011-65-0 ]
  • dimethyl 2-hydroxy-6H-benzofuro[2,3-b]indole-1,9-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With oxygen; copper(II) bis(trifluoromethanesulfonate); cobalt(II) chloride; In ethanol; at 40℃; under 760.051 Torr; for 48h;Sealed tube; Add 2-methyl carboxylate to phenol (0.2 mmol, 1.0 equiv.), 5-methyl carboxylate indole (0.2 mmol, 1.0 equiv.), and CoCl2 (1.3 mg, 5 mol%) in a 25ml sample bottle. , Cu(OTf)2 (7.3mg, 10mol%) and magnets, sealed with a rubber stopper, vacuumed and then filled with O2, transferred 4ml of 95% ethanol with a syringe to a sealed sample bottle, and then put the bottle inside The atmosphere was communicated with 1atm O2. After the reaction was stirred at 40C for 48h, the solvent was removed by blowing air at a constant temperature of 30C for 1 hour. The residue was purified by column chromatography on silica gel. The eluent was petroleum ether/ethyl acetate 20: 1 to 5:1 gradient elution. The target product was collected, and the isolated yield was 60%
 

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Technical Information

Categories

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