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Chemical Structure| 128742-76-7

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Product Details of [ 128742-76-7 ]

CAS No. :128742-76-7
Formula : C11H11NO2
M.W : 189.21
SMILES Code : O=C(C1=CC2=C(N(C)C=C2)C=C1)OC
MDL No. :MFCD11977801
InChI Key :VJJMGOYLSMSMCD-UHFFFAOYSA-N
Pubchem ID :10679201

Safety of [ 128742-76-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 128742-76-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 9
Fraction Csp3 0.18
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 54.48
TPSA ?

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

31.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.35
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

1.85
Log Po/w (WLOGP)?

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

1.96
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.

1.67
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

1.79
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.

-2.52
Solubility 0.568 mg/ml ; 0.003 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.

-2.13
Solubility 1.41 mg/ml ; 0.00747 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

-2.92
Solubility 0.225 mg/ml ; 0.00119 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.

-6.14 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)

1.35

Application In Synthesis of [ 128742-76-7 ]

* 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 [ 128742-76-7 ]

[ 128742-76-7 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 79-37-8 ]
  • [ 128742-76-7 ]
  • 3-Chlorooxalyl-1-methyl-1H-indole-5-carboxylic acid methyl ester [ No CAS ]
  • 2
  • [ 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.

  • 3
  • [ 128742-76-7 ]
  • [ 113-00-8 ]
  • <i>N</i>-(1-methyl-1<i>H</i>-indole-5-carbonyl)-guanidine [ No CAS ]
  • 4
  • [ 1670-81-1 ]
  • [ 74-88-4 ]
  • [ 128742-76-7 ]
YieldReaction ConditionsOperation in experiment
93% With sodium hydride; In N,N-dimethyl-formamide; at 20℃; for 24h; A solution of 1H-indole-5-carboxylic acid (1.6 g, 10 mmol), sodium hydride (1.2 g, 30 mmol), iodomethane (6.2 mL, 100 mmol) and DMF (40 mL) was stirred and room temperature for 24 hr. The reaction mixture was then quenched with water (5 mL) and diluted with ether (150 mL) and ethyl acetate (50 mL). After washing with aq. NH4Cl (100 mL), water (100 mL) and then brine (100 mL), the organic layer was dried over MgSO4, filtered and concentrated. The remaining material was subjected to flash chromatography (ethyl acetate/hexane 1:4) to provide 1-methyl-1H-indole-5-carboxylic acid methyl ester as a crystalline solid (1.77 g, 93% yield). 1H NMR (400 MHz, CDCl3) delta 8.40 (s, 1H), 7.94 (d, 1H, J=9.0 Hz), 7.34 (d, 1H, J=9.0 Hz), 7.12 (d, 1H, J=2.9 Hz), 6.60 (d, 1H, J=2.9 Hz), 3.94 (s, 3H), 3.83 (s, 3H).
93% A solution of l//-indole-5-carboxylic acid (1.6 g, 10 mmol), sodium hydride (1.2 g, 30 mmol), iodomethane (6.2 mL, 100 mmol) and DMF (40 mL) was stirred and room temperature for 24 hr. The reaction mixture was then quenched with water (5 mL) and diluted with ether (150 mL) and ethyl acetate (50 mL). After <n="94"/>washing with aq. NH4Cl (100 mL), water (100 mL) and then brine (100 mL), the organic layer was dried over MgSO4, filtered and concentrated. The remaining material was subjected to flash chromatography (ethyl acetate/hexane 1:4) to provide 1 -methyl- l//-indole-5-carboxylic acid methyl ester as a crystalline solid (1.77 g, 93% yield). 1H NMR (400 MHz, CDCl3) delta 8.40 (s, IH), 7.94 (d, IH, J = 9.0 Hz), 7.34 (d, IH, J = 9.0 Hz), 7.12 (d, IH, J = 2.9 Hz), 6.60 (d, IH, J = 2.9 Hz), 3.94 (s, 3H), 3.83 (s, 3H).
66.43% With sodium hydride; In N,N-dimethyl-formamide; for 1h;Inert atmosphere; Cooling with ice; In the atmosphere of nitrogen and ice bath conditions,Compound 5-carboxylic acid hydrazine (0302-104) (1 g, 6.2 mmol, 1 eq.)Dissolved in 10 ml of DMF,Sodium hydride (744 mg, 18.6 mmol, 3 eq) was slowly added.After stirring the mixture for 15 minutes,Methyl iodide (2.2 g, 15.5 mmol, 2.5 eq.) was added dropwise thereto.The mixture was stirred at ice bath for 1 hour. After the reaction is completed, add water to quench and filter to obtain the targetCompound 1-methyl-1H-indole-5-carboxylic acid methyl ester (780 mg, yield: 66.43%) was a yellow solid.
56% To a stirred suspension of 0.99 g (24.8 mmol) of sodium hydride (60% oil dispersion), which had been previously washed 3X with hexanes, in anhydrous DMF (50 mL) is added lH-indole-5-carboxylic acid (2.0 g, 12.4 mmol). The mixture is stirred at rt for 30 min and methyl iodide (3.09 mL, 49.7 mmol) is added. The mixture is stirred overnight and diluted with water, extracted with EtOAc (3x). The combined organic layers are washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product is purified by flash chromatography on silica gel. Elution with hexanes-EtOAc (90: 10) gives methyl 1-METHYL-LH-INDOLE-5-CARBOXYLATE as a white solid (1.32 g, 56%) : LH NMR (400 MHz, CDC13) 8 8.44, 7.97, 7. 37, 7D6, 6.63, 3.97, 3.87.
With NaH; In water; N,N-dimethyl-formamide; (192-1) Under nitrogen atmosphere, a solution of indole-5-carboxylic acid (1.05 g) in DMF (40 mL) was cooled to 0 C., and thereto was added NaH (544 mg, 60%), and the mixture was stirred at the same temperature for 10 minutes, and stirred at room temperature for 30 minutes. The mixture was cooled to 0 C., and thereto was added iodomethane (3.68 g), and the mixture was stirred at room temperature for 48 hours. Water was added to the mixture, and the mixture was extracted three times with ethyl acetate-toluene, and dried over MgSO4. The solvent was evaporated under reduced pressure to give a crude methyl 1-methylindole-5-carboxylate.
With NaH; In water; N,N-dimethyl-formamide; (192-1) Under nitrogen atmosphere, a solution of indole-5-carboxylic acid (1.05 g) in DMF (40 mL) was cooled to 0C, and thereto was added NaH (544 mg, 60 %), and the mixture was stirred at the same temperature for 10 minutes, and stirred at room temperature for 30 minutes. The mixture was cooled to 0C, and thereto was added iodomethane (3.68 g), and the mixture was stirred at room temperature for 48 hours. Water was added to the mixture, and the mixture was extracted three times with ethyl acetate-toluene, and dried over MgSO4. The solvent was evaporated under reduced pressure to give a crude methyl 1-methylindole-5-carboxylate.
To a solution of indole-carboxylic acid (5 g, 1 eq.) in DMF (250 ml) was added dry NaH (3.75 g, 5 eq.), freshly prepared by washing 60% NaH in mineral oil with hexane. After the mixture was stirred at room temperature for 40 minutes, iodomethane (20 mL, 10 eq.) was added. After being stirred for 20 hours, the reaction mixture was poured into a IM NaHSO4 aqueous solution (30 mL), and extracted with ethyl acetate. The organic layer was back-extracted sequentially with water, a saturated aqueous NaHCtheta3 solution, dried over MgSO4, filtered, and concentrated to afford a crude product as an oil 1-37.

  • 5
  • [ 128742-76-7 ]
  • [ 186129-25-9 ]
YieldReaction ConditionsOperation in experiment
97% With water; sodium hydroxide; In tetrahydrofuran; at 40℃; for 4h; Preparation of 1 -methyl -1 W-indole-5-carboxylic acid To a solution of methyl 1 ~methyj-1H-ndoSe~5-carboxylate (500 mg, 2.64 mmol) in THF/H20 (2 mL/2 mL) was added NaOH (635 mg, 15.9 mmol). The mixture was stirred at 40 C for 4 hours. Then the reaction liquid was concentrated in vacuoio remove most of organic solvent, and H0 (10 mL) was added to the residue. The mixture was acidified (pH 5-6) with HCI (cone.) and the resulting precipitate was collected as the target (450 mg, 97%). LCMS: m/z 176.1 [M+Hf
96% With hydrogenchloride; sodium hydroxide; In THF (50 mL)-MeOH; To a solution of the crude <strong>[128742-76-7]methyl 1-methylindole-5-carboxylate</strong> in THF (50 mL)-MeOH (50 mL) was added a 6N NaOH solution (5.4 mL), and the mixture was stirred at room temperature for 144 hours. The solvent was evaporated under reduced pressure. The residue was washed with ethyl acetate, and thereto was added a 6N aqueous hydrochloric acid solution to adjust the pH value thereof to pH=5-6. The mixture was extracted twice with ethyl acetate, and dried over MgSO4. The solvent was evaporated under reduced pressure to give 1-methyl-1H-indol-5-carboxylic acid (1.08 g, 96%). 1H NMR (DMSO-d6, 400 MHz) delta 12.42 (brs, 1H,), 8.23 (d, 1H, J=1.2 Hz), 7.76 (dd, 1H, J=8.6, 1.2 Hz), 7.50 (d, 1H, J=8.6 Hz), 7.43 (d, 1H, J=3.1 Hz), 6.57 (dd, 1H, J=3.1, 0.7 Hz), 3.82 (s, 3H).
96% With hydrogenchloride; sodium hydroxide; In THF (50 mL)-MeOH; To a solution of the crude <strong>[128742-76-7]methyl 1-methylindole-5-carboxylate</strong> in THF (50 mL)-MeOH (50 mL) was added a 6N NaOH solution (5.4 mL), and the mixture was stirred at room temperature for 144 hours. The solvent was evaporated under reduced pressure. The residue was washed with ethyl acetate, and thereto was added a 6N aqueous hydrochloric acid solution to adjust the pH value thereof to pH=5-6. The mixture was extracted twice with ethyl acetate, and dried over MgSO4. The solvent was evaporated under reduced pressure to give 1-methyl-1H-indol-5-carboxylic acid (1.08 g, 96 %). 1H NMR (DMSO-d6, 400MHz) delta 12.42 (brs, 1H,), 8.23 (d, 1H, J=1.2Hz), 7.76 (dd, 1H, J=8.6, 1.2Hz), 7.50 (d, 1H, J=8.6Hz), 7.43 (d, 1H, J=3.1Hz), 6.57 (dd, 1H, J=3.1, 0.7Hz), 3.82 (s, 3H).
94% To a stirred solution of methyl L-METHYL-LH-INDOLE-5-CARBOXYLATE (500 mg, 2.65 mmol) in MEOH (5 mL) is added sodium hydroxide (20 mL of a 2.5% aqueous solution). The mixture is heated at 80C for 1.5 h and MEOH is removed in vacuo. The remaining aqueous solution is acidified with 1 N aqueous HC1 to pH = 2. The resulting precipitate is collected by filtration, washed with water and dried in vacuo to afford 1-METHYL-LH-INDOLE-5-CARBOXYLIC acid as a white solid (437 mg, 94%) : LH NMR (400 MHz, DMSO-d6) 8 12. 44,8. 23,7. 75,7. 50,7. 44,6. 57,3. 83.
In sodium hydroxide; ethanol; Step B. 1-Methyl-indole-5-carboxylic Acid A solution of <strong>[128742-76-7]1-methyl-indole-5-carboxylic acid methyl ester</strong> of Step A (2.5 g, 13.2 mmol) in ethanol (40 mL) containing 2.5N aqueous NaOH (3:1, v/v) was heated at reflux for one hour. The reaction mixture was concentrated in vacuo, and the residue partitioned between diethyl ether and 1N HCl. The organic layer was washed with brine, dried over sodium sulfate, and evaporated to dryness to provide the title compound as an off-white solid (1.82 g). NMR (DMSO-d6, 300 MHz): delta 3.82 (s, 3H), 6.58 (dd, 1H), 7.42 (d, 1H), 7.48 (d, 1H), 7.75 (d, 1H), 8.22 (s, 1H), 12.38 (broad s, 1H).
In sodium hydroxide; ethanol; Step B. 1-Methyl-indole-5-carboxylic acid A solution of <strong>[128742-76-7]1-methyl-indole-5-carboxylic acid methyl ester</strong> of Step A (2.5 g, 13.2 mmol) in ethanol (40 mL) containing 2.5N aqueous NaOH (3:1, v/v) was heated at reflux for one hour. The reaction mixture was concentrated in vacuo, and the residue partitioned between diethyl ether and 1N HCl. The organic layer was washed with brine, dried over sodium sulfate, and evaporated to dryness to provide the title compound as a off-white solid (1.82 g). NMR (DMSO-d6, 300 MHz): delta 3.82 (s, 3H), 6.58 (dd, 1H), 7.42 (d, 1H), 7.48 (d, 1H), 7.75 (d, 1H), 8.22 (s, 1H), 12.38 (broad s, 1H)
To a solution of the crude product 1-37 in THF (80 mL) was added 80 mL of a 1 M LiOH aqueous solution. The mixture was stirred at 500C for 24 hours and then diluted with diethyl ether. After the mixture was then extracted twice with a saturated NaHCtheta3 aqueous solution, 6 M HCl was added to the combined aqueous layers to adjust the pH to 1. The aqueous layer was then extracted with ethyl acetate. The combined ethyl acetate layer was dried over Na2SO4, filtered, and concentrated to give compound 1-38 (4.72 g, 87%). 1H NMR (CDCl3) delta 8.49 (s, IH), 8.01-7.98 (dd, J = 8.4 Hz, 1.5 Hz, IH), 7.38-7.35 (d, J = 8.7 Hz, IH), 7.14-7.13 (d, J = 3.0 Hz, IH), 6.63 (d, J = 3.0 Hz, IH), 3.84 (s, 3H). ESI-MS (M+H+) = 176.
To the solution of 53 (4.90 g, 25.89 mmol) in THF/H2O was added 1N NaOH and the resulting mixture was heated at reflux for 60 min. The reaction mixture was cooled to 0 C., acidified with 1N HCl to ca. pH=3, and the mixture was partitioned between H2O and EtOAc and the combined organic layers were dried (MgSO4), filtered and concentrated to afford 4.25 g of 1-methyl-1H-indole-5-carboxylic acid (55).
With sodium hydroxide; In ethanol; water; for 1h;Heating / reflux; Step B. 1-Methyl-indole-5-carboxylic acid. A solution of <strong>[128742-76-7]1-methyl-indole-5-carboxylic acid methyl ester</strong> of Step A (2.5 g, 13.2 mmol) in ethanol (40 mL) containing 2.5 N aqueous NaOH (3:1, v/v) was heated at reflux for one hour. The reaction mixture was concentrated in vacuo, and the residue partitioned between diethyl ether and 1N HCl. The organic layer was washed with brine, dried over sodium sulfate, and evaporated to dryness to provide the title compound as a off-white solid (1.82 g). NMR (DMSO-d6, 300 MHz): delta 3.82 (s, 3H), 6.58 (dd, 1H), 7.42 (d, 1H), 7.48 (d, 1H), 7.75 (d, 1H), 8.22 (s, 1H), 12.38 (broad s, 1H).

  • 6
  • [ 128742-76-7 ]
  • [ 78-94-4 ]
  • 1-methyl-3-(3-oxo-butyl)-1<i>H</i>-indole-5-carboxylic acid methyl ester [ No CAS ]
  • 7
  • [ 128742-76-7 ]
  • [ 100-11-8 ]
  • [ 950763-40-3 ]
YieldReaction ConditionsOperation in experiment
58% With silver(l) oxide; In 1,4-dioxane; for 121h;Heating / reflux; A solution of l-methyl-l//'-indole-5-carboxylic acid methyl ester (0.38 g, 2.0 mmol), prepared using procedures as described in Example 1, Ag?O (0.51 g, 2.2 mmol), 4-nitro-benzyl bromide (0.48 g, 2.2 mmol) and dioxane (6 mL) was heated to reflux for 25 hr, then more 4-nitro-benzyl bromide (0.48 g, 2.2 mmol) was added and the solution was heated at reflux an additional 4 days. After cooling to room temperature, the reaction mixture was diluted with ether (50 mL) and ethyl acetate (50 mL), washed with aq. NH4Cl (50 mL) and then brine (50 mL). The organic layer was dried over MgSO4, filtered and concentrated. The remaining residue was subjected to flash chromatography (ethyl acetate/hexane, 1:4) to provide of l-methyl-3-(4-nitro-phenylmethyl)-l//-indole- 5-carboxylic acid methyl ester (0.38 g, 58% yield). 1H NMR (400 MHz, CDCl3) delta 8.26 (s, IH), 8.16 (d, 2H, J= 8.3 Hz), 7.98 (d, IH, J= 8.3 Hz), 7.45 (d, 2H, J= 8.3 Hz), 7.35 (d, IH, J= 8.3 Hz), 6.90 (s, IH), 4.25 (s, 2H), 3.94 (s, 3H), 3.82 (s, 3H).
  • 8
  • [ 128742-76-7 ]
  • [ 459-46-1 ]
  • [ 950763-44-7 ]
YieldReaction ConditionsOperation in experiment
22% With silver(l) oxide; In 1,4-dioxane; for 20h;Heating / reflux; A solution of l-methyl-l/Z-indole-S-carboxylic acid methyl ester (0.17 g, 0.9 mmol), prepared using procedures as described in Example 1, Ag2O (0.22 g, 0.95 mmol), 4-fiuoro-benzyl bromide (0.18 g, 0.95 mmol) and dioxane (4 mL) were heated to reflux for 16 hr, then more 4-fiuoro-benzyl bromide (90 mg, 0.5 mmol) was added and the solution was heated at reflux an additional 4 hr. After cooling to room temperature, the reaction mixture was diluted with ether (60 mL), washed with aq. NH4Cl (50 mL) and then brine (50 mL). The organic layer was dried over MgSO4, filtered and concentrated. The remaining residue was subjected to flash chromatography (ethyl acetate/hexane, 1:3) to provide 3-(4-fluoro-phenylmethyl)-l-methyl-l//-indoIe-5-carboxylic acid methyl ester (58 mg, 22% yield).
  • 9
  • [ 924-44-7 ]
  • [ 128742-76-7 ]
  • methyl 3-(2-ethoxy-1-hydroxy-2-oxoethyl)-1-methylindole-5-carboxylate [ No CAS ]
  • methyl 3-(2-ethoxy-1-hydroxy-2-oxoethyl)-1-methylindole-5-carboxylate [ No CAS ]
  • 10
  • [ 119072-54-7 ]
  • [ 128742-76-7 ]
  • 3-[(2,6-dimethylphenylimino)-methyl]-1-methyl-1H-indole-5-carboxylic acid methyl ester [ No CAS ]
  • 11
  • [ 128742-76-7 ]
  • [ 884507-16-8 ]
  • 12
  • [ 128742-76-7 ]
  • 1-methyl-1<i>H</i>-indole-5-carbonyl azide [ No CAS ]
  • 13
  • [ 128742-76-7 ]
  • 8,8-dimethoxy-6-dimethoxymethyl-3-methylpyrrolo[3,2-e]indol-7(3H,6H,8H)-one [ No CAS ]
  • 14
  • [ 128742-76-7 ]
  • 1-(bis(propylthio)methyl)-6-methyl-3,3-bis(propylthio)pyrrolo[2,3-e]indol-2(1H,3H,6H)-one [ No CAS ]
  • 15
  • [ 1670-81-1 ]
  • [ 128742-76-7 ]
  • 16
  • [ 128742-76-7 ]
  • [ 884847-77-2 ]
  • 17
  • [ 128742-76-7 ]
  • 1-methyl-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-oxazol-2-yl]-1<i>H</i>-indole [ No CAS ]
  • 18
  • [ 128742-76-7 ]
  • 1-methyl-1H-indole-5-carboxylic acid N-[2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]amide [ No CAS ]
  • 20
  • [ 128742-76-7 ]
  • [ 131305-28-7 ]
  • 21
  • [ 128742-76-7 ]
  • [ 137494-44-1 ]
  • 22
  • [ 128742-76-7 ]
  • [ 137467-12-0 ]
  • 23
  • 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
YieldReaction ConditionsOperation in experiment
93% With sodium hydride; In N,N-dimethyl-formamide; at 0 - 50℃; for 8h; General procedure: 1H-indole-5-carboxylic acid methyl ester (1 g, 5.71 mmol) was dissolved in dimethylformamide (20 mL), and isopropyl iodide (1.14 mL, 11.42 mmol) and sodium hydride (205 mg, 8.56 mmol) were slowly added dropwise thereto at 0. The mixture was stirred at 50 for 8 hours, added with 1N hydrochloric acid solution and extracted with ethyl acetate. The extract was washed with brine, dried with anhydrous magnesium sulfate and filtered. The filtrate was distilled under reduced pressure and separated by column chromatography to obtain the title compound (1.1 g, 89%).[326] NMR: 1H-NMR (400HMz, CDCl3); delta 8.39 (s, 1H), 7.90(dd, 1H), 7.37(d, 1H), 7.27(d, 1H), 6.60(d, 1H), 4.70(m, 1H), 3.93(s, 3H), 1.54(d, 6H)
(1) Methyl 1-methyl-5-indolecarboxylate: 1H NMR (CDCl3) delta: 3.82 (3H, s), 3.93 (3H, s), 6.8 (1H, dd, J=1.0, 3.3 Hz), 7.11 (1H, d, J=3.3 Hz), 7.32 (1H, d, J=8.6 Hz), 7.91-7.95 (1H, m), 8.39-8.40 (1H, m).
  • 25
  • [ 50-01-1 ]
  • [ 128742-76-7 ]
  • 1-methyl-5-indoloylguanidine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium methylate; In methanol; EXAMPLE 2 Preparation of 1-methyl-5-indoloylguanidine hydrochloride The reaction was carried out in a manner similar to Example 1 except for using 1.00 g (5.29 mmol) of methyl 1-methyl-5-indolecarboxylate, 5.05 g (52.9 mmol) of guanidine hydrochloride and 50 ml of a methanol solution of 2.85 g (52.9 mmol) of sodium methoxide. Thus 0.92 g (68.9%) of 1-methyl-5-indoloylguanidine hydrochloride was obtained. M.P.: 260 C. or higher 1H NMR (DMSO-d6) delta: 3.86 (3H, s), 6.62-6.64 (1H, m), 7.50 (1H, d, J=3.3 Hz), 7.61 (1H, d, J=8.9 Hz), 7.91-7.95 (1H, m), 8.44 (2H, br-s), 8.47 (1H, d, J=1.3 Hz), 8.7 (2H, br-s), 11.7 (1H, br-s).
  • 26
  • [ 128742-76-7 ]
  • [ 1158209-28-9 ]
YieldReaction ConditionsOperation in experiment
i) 3-Chlorosulfonyl-<strong>[128742-76-7]1-methyl-1H-indole-5-carboxylic acid methyl ester</strong> This compound was prepared in analogy to the procedure described in Example 6i) starting from <strong>[128742-76-7]1-methyl-1H-indole-5-carboxylic acid methyl ester</strong> (Robert John; Failli, Amedeo Arturo, WO 2000046228) to obtain the desired compound as a yellow solid. MS (ISP): m/e 287.8 (M+H)+
  • 27
  • [ 128742-76-7 ]
  • [ 1235085-81-0 ]
  • 28
  • [ 128742-76-7 ]
  • [ 67-68-5 ]
  • [ 1313759-53-3 ]
  • 29
  • [ 128742-76-7 ]
  • [ 851211-79-5 ]
YieldReaction ConditionsOperation in experiment
24% With hydrazine hydrate; In ethanol; for 18h;Heating; Preparation of 1-methyl 1H-indole-5-carboxylic acid hydrazide To 1.0 g (5.3 mmol) of the 1-methyl 1H-benzimidazole 5-carboxylic acid methyl ester, dissolved in 20 ml of ethanol, 20 ml (400mml) of hydrated hydrazine (100%) are added. The solution is heated for 18 hours After concentration, the concentrate is dissolved in water, alkanized with ammoniac (20%) to basic pH and filtrated the concentrate is then washed with water and vacuum desiccated. 240 mg of a white powder is obtained (R=24%). RMN 1H (DMSO-d6, 300 MHz) delta : 3.79 (s, 3H), 4.43 (bs,2H), 6.49 (d, J=2.9 Hz, 1H), 7.38 (d, J=3.1 Hz,1H), 7.44 (d, J=8.6 Hz, 1H), 7.66 (dd, J=8.6 Hz, J=1.5 Hz, 1H), 8.08(d, J= 1.5 Hz,1H), 9.60 (bs, 1H).
  • 30
  • [ 1352622-01-5 ]
  • [ 1352622-18-4 ]
  • [ 128742-76-7 ]
YieldReaction ConditionsOperation in experiment
40%; 45% With triethyl borane; oxygen; N-ethylpiperidinium hypophosphite; In 1,4-dioxane; hexane; at 73℃; for 2h;Air atmosphere; General procedure: To a stirring solution of N-methylated substrate (0.1-0.6 mmol, 1.0 eq.) in dioxane (0.034 M) at 73 C was added BEt3 (1 M sol?n in hexanes, 0.25 eq.) and EPHP (2.5 eq. dissolved in dioxane [c = 0.084 M]) simultaneously via syringe pump over 2 h. Upon complete addition of reagents, the reaction mixture was allowed to cool to rt, dissolved in Et2O (50 mL) and washed with 1 M K2CO3 (2 × 20 mL). The organic fractions were combined, dried over MgSO4, filtered and concentrated in vacuo to give a brown oil which was purified by flash chromatography to afford the indole products 7a to 7j.
  • 31
  • [ 1352621-86-3 ]
  • [ 18358-63-9 ]
  • [ 1352622-18-4 ]
  • [ 128742-76-7 ]
  • 32
  • [ 619-45-4 ]
  • [ 1352622-18-4 ]
  • [ 128742-76-7 ]
  • 33
  • [ 128742-76-7 ]
  • [ 68-12-2 ]
  • [ 1313759-53-3 ]
YieldReaction ConditionsOperation in experiment
31% With copper(l) iodide; oxygen; trifluoroacetic acid; at 130℃; under 760.051 Torr; for 36h;Schlenk technique; Sealed tube; General procedure: A 100 mL sealed Schlenk tube equipped with a magnetic stir bar and charged with CuI (1 equiv,0.2 mmol) was evacuated and back filled with oxygen (this process was repeated 3 times). And then indole (0.2 mmol), CF3COOH (1.2 equiv, 0.24 mmol) DMF(1 mL) were added. The reaction mixture was stirred at 130 oC, after completion as monitored by TLC and GC, the reaction was cooled to room temperature. After addition of aqueous NH3 solution, the reaction mixture was extracted with EtOAc (3×5ml). The combined organic layers were dried over NaSO4, filtered and concentrated. The residue was purified by flash columnchromatography on silica gel to give the analitycally pure product.
  • 34
  • [ 128742-76-7 ]
  • [ 611-10-9 ]
  • [ 98-80-6 ]
  • methyl 3-(2-(ethoxycarbonyl)-3-oxocyclopentyl)-1-methyl-2-phenyl-1H-indole-5-carboxylate [ No CAS ]
  • 35
  • [ 128742-76-7 ]
  • [ 256935-90-7 ]
 

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Technical Information

Categories

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[ 128742-76-7 ]

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