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Chemical Structure| 948-65-2

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Product Details of [ 948-65-2 ]

CAS No. :948-65-2
Formula : C14H11N
M.W : 193.24
SMILES Code : N1C(=CC2=C1C=CC=C2)C1=CC=CC=C1
MDL No. :MFCD00005608
InChI Key :KLLLJCACIRKBDT-UHFFFAOYSA-N
Pubchem ID :13698

Safety of [ 948-65-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H318-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P310-P332+P313-P362-P403+P233-P405-P501

Computational Chemistry of [ 948-65-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 15
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 63.73
TPSA ?

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

15.79 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.2
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

-0.54
Log Po/w (WLOGP)?

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

3.83
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.

3.06
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

4.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.54

Water Solubility

Log S (ESOL):?

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

-1.37
Solubility 8.21 mg/ml ; 0.0425 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.

0.68
Solubility 920.0 mg/ml ; 4.76 mol/l
Class?

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

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

-5.8
Solubility 0.000304 mg/ml ; 0.00000157 mol/l
Class?

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

Moderately 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

Yes
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.

-7.86 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

2.0
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)

1.73

Application In Synthesis of [ 948-65-2 ]

* 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 [ 948-65-2 ]

[ 948-65-2 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 948-65-2 ]
  • [ 100-97-0 ]
  • [ 25365-71-3 ]
YieldReaction ConditionsOperation in experiment
88% With silica supported ceric ammonium nitrate; In acetonitrile; for 12h;Reflux; General procedure: a mixture of indole (1 mmol), HMTA (2.5 mmol), and 10% CAN-SiO2 was refluxed in CH3CN (5.0 mL). After the reaction was complete, the mixture was evaporated to give a crude residue of CAN-SiO2 and product. The crude residue was washed with EtOAc (10 mL 5) and dried to leave a crude product that was purified by short flash column chromatography (EtOAc/hexane = 1:3).
77% With aluminum (III) chloride; In N,N-dimethyl-formamide; at 120℃; for 2h; General procedure: A method for synthesizing compound III-1 wherein R1, R2 and R3 are simultaneously hydrogen in the formula III, the method comprising the steps of:(1) Add to a 50 mL round bottom flask1.0mmol indole(In the formula I, R1, R2, and R3 are both hydrogen) and1.0 mmol (0.140 g) of hexamethylenetetramine, then 2 mL of N,N-dimethylformamide (DMF), stirred in a magnetic stirrer to dissolve the solid, followed by the addition of 0.05 mmol (0.012 g) of crystalline trichloride Aluminum, connected to a reflux condenser, heated at 120 C, the reaction progress was monitored by TLC, and the reaction was cooled to room temperature after 1 h to prepare a suspension;(2) The suspension prepared in the step (1) is suction filtered with a funnel padded with diatomaceous earth.The filter cake was washed well with ethyl acetate, suction filtered, and the above operation was repeated until the filtrate had no product, and all the filtrates were combined.Dilute with 15 mL of saturated saline solution, disperse and separate the layers, and the aqueous layer was further extracted with ethyl acetate three times.Each time 10 mL, the ethyl acetate layer was combined and washed with 10 mL of 2 mol/L diluted hydrochloric acid.Wash with 10 mL of saturated sodium bicarbonate solution, and finally wash with 10 mL of saturated brine.The washed ethyl acetate layer was dried over anhydrous sodium sulfate, and after drying, the desiccant was filtered off.Then use a rotary evaporator to recover the solvent to concentrate the product, and finally,The residue is subjected to silica gel column chromatography using a mixture of n-hexane-ethyl acetate (V/V = 2:1) as an eluent to obtain a purified product.The mass of the compound III-indole-3-carbaldehyde is 0.137g,The product yield was 94%.
70% With iodine; oxygen; pyrographite; In N,N-dimethyl-formamide; at 120℃; for 4h; General procedure: A 50 mL round bottom flask equipped with a magnetic stirring bar was charged with substituted indole 1 (1.0 mmol, 1.0 equiv), HMTA (2.0 mmol, 0.2803 g, 2.0 equiv), activated carbon (0.1 g) and DMF (2 mL). Then I2 (0.2 mmol, 0.0507g, 20 mol%) was added and the flask was equipped with a reflux condenser. The reaction mixture was stirred at 120 oC under open air and monitored by TLC. Upon completion of the reaction, the reaction mixture was cooled to room temperature. The resultant mixture was filtered through a pad of celite and the filter cake was washed thoroughly with EtOAc (4 × 6 mL). The filtrate was washed with 0.5 M aqueous HCl (10 mL), saturated NaHCO3 solution (10 mL) and saturated NaCl solution ( 10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluted with hexane and ethyl acetate to give the product.
65% With water; iodine; In N,N-dimethyl-formamide; at 150℃; under 5171.62 Torr; for 0.133333h;Flow reactor; General procedure: The continuous flow reactor system consisted of the dual pump (KP-22-13, SS), PTFE tubing (length: 16 m, ID: 1 mm), T-junction (1.25 mm thru-hole), back pressure regulator (40, 75, 100, 250 psi), oil bath and hot plate. In this experiment, we used BOLA PTFE tubing to experiment at high temperature. In order to react stably at the temperature above the boiling point of water, looked for the maximum temperature conditions according to the pressure of the back pressure regulator in which the bubble does not occur. The reaction started in the concentration of indole (1.0 mmol), HMTA (2.0 mmol) and I 2 (1.0 mmol) in solvent (10 mL). Since this reaction proceeds in a single phase of liquid, the reaction time was set by the inner volume of tubing and the flow rate in the continuous flow reactor. After the reaction is over, the product was quantified using 1 H NMR and the NMR yield was obtained.

  • 2
  • [ 948-65-2 ]
  • [ 33513-42-7 ]
  • [ 25365-71-3 ]
YieldReaction ConditionsOperation in experiment
89% General procedure: Under nitrogen gas, phosphorous oxychloride (10 mmol) was added dropwise to dry dimethylformamide (DMF) (10 mmol) while cooling in an ice bath, and the reaction mixture was stirred for 1 h. A solution of compound 4 (1 mmol) in DMF (50 ml) was added dropwise to the mixture with continuous stirring, which was then heated to 70 C. The mixture was poured onto ice cold water (200 mL), naturalized with 40% NaOH, and extracted with chloroform. The chloroform extract was washed with water and dried over Na2SO4. The solvent was removed under vacuum. The residue was crystalized from an ethanol/water mixed solvent system.
89% With trichlorophosphate; at 70℃;Inert atmosphere; General procedure: Under nitrogen gas, phosphorous oxychloride (10 mmol) was added dropwise to dry dimethylformamide (DMF) (10 mmol) while cooling in an ice bath, and the reaction mixture was stirred for 1 h. A solution of compound 3 (1 mmol) in DMF (50 ml) was added dropwise to the mixture with continuous stirring, which was then heated to 70 C. The mixture was poured onto ice cold water (200 mL), naturalized with 40% NaOH, and extracted with chloroform. The chloroform extract was washed with water and dried over Na2SO4.The solvent was removed under vacuum. The residue was crystalized from an ethanol/water mixed solvent system [27]. 2-Phenyl-1H-indole-3-carbaldehyde (4a). Cream powder; Mp: 249-250 C; Yield: 89%; IR (KBr, cm-1): 3144 (NH), 2858(H-CO), 1625 (C=O), 1455 (C=C). 1H NMR (500 MHz, DMSO-d6) (δ, ppm): 7.24 (t, J = 7.9 Hz, 1H, H6), 7.29 (t, J = 7.9 Hz, 1H, H7), 7.51 (d, J = 7.9 Hz, 1H, H8), 7.56-7.62 (m, 3H, H3′,5′,4′), 7.78 (d, J = 9.3 Hz, 2H, H2′,6′), 8.21 (d, J = 7.9 Hz, 1H, H5), 9.96 (s, 1H, CHO), 12.40 (s, 1H, NH-indole). 13C NMR (125 MHz, DMSO-d6) (δ, ppm): 112.1, 113.5, 121.2, 122.5, 123.7, 125.8, 128.9, 129.2, 129.8, 130.1,135.9, 149.1, 185.5. Anal. Calcd. for C15H11NO: C, 81.43; H, 5.01; N, 6.33. Found: C, 81.53; H, 4.85; N, 6.45.
88% With trichlorophosphate; at 10 - 45℃; for 0.5h; General procedure: Compounds 10a-f were synthesized by known procedure. A solution of 2-aryl-1H-indole 9a-f (0.01 mol) in a minimum amount of DMF was added to the Vilsmeier-Haack reagent (was prepared from phosphorus oxychloride (1 mL) and DMF(3.15 mL)) maintaining the reaction temperature between 10 and 20 C. The reaction mixture was heated at 45 C for 30 min and poured into a mixture of ice-water (100 mL) and 10% aqueous NaOH (20 mL). The resulting mixture was refl uxed for 1 h and cooled to room temperature. The precipitate was collected by filtration, washed with water, dried, and recrystallized. 2-Phenyl-1H-indole-3-carbaldehyde (10a). White substance,yield 194 mg (88%), m.p. 236-240 C (dioxane) (cf. Ref. 33:m.p. 249-250 C). 1H NMR (DMSO-d6), δ: 7.41-7.21 (m, 2 H,H(5), H(6)); 7.52 (d, 1 H, H(7), J = 7.9 Hz); 7.67-7.56 (m, 3 H,H(3), H(4), H(5)); 7.85-7.76 (m, 2 H, H(2), H(6)); 8.23(d, 1 H, H(4), J = 7.5 Hz); 9.98 (s, 1 H, CHO); 12.43 (s, 1 H,NH). 13C NMR (DMSO-d6), δ: 112.5 (C(3)), 113.9 (C(7)),121.5 (C(5)), 122.9 (C(6)), 124.2 (C(4)), 126.2 (C(2)), 129.5(2 C, C(2), C(6)); 130.2 (C(3a)), 130.3 (C(4)), 130.4 (2 C, C(3),C(5)); 136.4 (C(1)), 149.6 (C(7a)), 186.0 (CHO). MS (ESI), m/z:244.0731 [M + Na]+. C15H11NNaO. Calculated: M = 244.0733.
78% General procedure: Into a 25 mL tube, Ph3P (0.75 mmol, 1.5 equiv.), ICH2CH2I (0.75 mmol, 1.5 equiv.)indoles 1 (0.5 mmol, 1 equiv.), DMAP (0.5 mmol, 1 equiv.), and DMF (2 mL) wereadded under air atmosphere. The resulting mixture was stirred at 80 oC for 2 hours. H2O(5 mL) was added and stirred at 80 oC for another 2 hours. The mixture was cooled toroom temperature. A saturated aqueous brine solution was added, and the crude organicproduct was extracted by CH2Cl2. The combined organic phase was dried withanhydrous Na2SO4. After filtration, the solution was concentrated under reducedpressure to remove the solvent. The residue was subjected to flash columnchromatography on silica gel (pentane/ethyl acetate) to give the pure pro ducts 4j-4u.
[0271] A mixture of DMF (11.0 mL, 142 mmol) and phosphorous oxychloride (3.63 mL, 39 mmol) is stirred at 0 C. for 1 h, a 0.2 mL portion is pipetted into a solution of 2-phenylindole (96 mg, 0.5 mmol) in DMF at 5 C. This reaction mixture is stirred at 5-10 C. for 1 h, quenched with water, stored at -200 for 16 h and filtered. The filtercake is washed with water and dried in vacuo to afford the 2-phenylindole-3-carboxaldehyde intermediate. A suspension of the thus-obtained 2-phenylindole-3-carboxaldehyde (44.2 mg, 0.2 mmol) in isopropanol and concentrated HCl (50 μL) is treated with aminoguanidine bicarbonate (27 mg, 0.2 mmol), heated at 80 C. for 2 h, cooled to room temperature and concentrated in vacuo. The resultant residue is purified by HPLC to afford the title product, 28 mg (20% yield), identified by mass spectral and HPLC analyses (M+H) 277; retention time 3.76 min. 1HPLC conditions: Hewlett Packard 1100; YMC ODS-A 4.6 mm×50 mm 5 u column at 23 C.; 10 uL injection; Solvent A: 0.05% TFA/water; Solvent B: 0.05% TFA/acetonitrile; Gradient: Time 0: 98% A; 1 min: 98% A; 7 min: 10% A, 8 min: 10% A; 8.9 min: 98% A; Post time 1 min. Flow rate 2.5 mUmin; Detection: 220 and 254 nm DAD.
General procedure: P-substituted acetophenone (2mmol) and phenyl-hydrazine (2mmol) were poured into a round bottom flask, then CH3COOH (0.5mL) and CH4O3S (27mmol) were added. After the thin layer chromatography (TLC) monitoring reaction was completed, the intermediate 3 was obtained by pouring the mixture into ice water. At -30C, POCl3 (10mmol) was slowly added dropwise to a round bottom flask containing DMF (10mmol), and the reaction was stirred for 1h. After that, intermediate 3 (1mmol) was dissolved in DMF, slowly added dropwise to the flask, and the reaction was heated to 70C with stirring. Monitor the reaction through the TLC. Finally, the mixture was poured into ice water, washed with 40% NaOH solution, and then extracted with DCM to obtain intermediate 4.
With Vilsmeier reagent; trichlorophosphate; at 0℃; for 2h; Compound 4 (5.5mmol, 1eq) was added to the Vilsmeier-haack reagent prepared by the addition of POCl3 (3.8eq) in DMF (5.1mmol of 4) at 0C. The mixture was stirred at 0C for 2 hrs to ensure the complete consumption of starting material by TLC monitoring. Then reaction was quenched slowly by adding ice and neutralized the reaction mixture by adding the 37% of NaOH solution. The resulting precipitate was filtered and dried to afford the 2-Phenylindole-3-carboxaldehyde (5) in good yield.

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  • 3
  • [ 948-65-2 ]
  • [ 50606-58-1 ]
  • [ 244086-73-5 ]
  • 5
  • [ 108-86-1 ]
  • [ 143360-89-8 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • [ 2415-33-0 ]
  • 6
  • [ 17763-67-6 ]
  • [ 143360-89-8 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • 7
  • [ 108-86-1 ]
  • [ 143360-89-8 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • 8
  • [ 108-86-1 ]
  • [ 125345-25-7 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • 9
  • [ 948-65-2 ]
  • [ 25365-71-3 ]
YieldReaction ConditionsOperation in experiment
93% 1.7 g of POCl3 was added drop wise to a solution of 2-phenyindole (1.93 g) in 20 mL of DMF, at 10 C. The mixture was stirred at 50 C. for 1 hr, cooled and diluted with saturated NaHCO3. The suspension was heated at 60 C. for 15 min, cooled, the precipitates of 2-phenylindol-3-carboxaldehyde were filtered. Yield 2.05 g (93%). The mixture of phenanthroquinoline (0.105 g) and 2-phenylindol-3-carboxaldehyde (0.111 g) was refluxed in 3 mL of acetic acid in the presence of 0.39 g of ammonium acetate for 1.5 hrs. The red colored solution was poured in water (100 ml) and washed with DCM (3×40 ml). The aqueous layer was then neutralized with saturated aqueous solution of NA2CO3, the solid obtained was filtered, washed with EtOH and crystallized from DMF: EtOH:H2O=1:1:1. A purified solid 0.12 g was achieved, with a yield of 58%.
  • 10
  • [ 948-65-2 ]
  • [ 79-37-8 ]
  • [ 925-90-6 ]
  • [ 78190-11-1 ]
  • [ 256446-54-5 ]
YieldReaction ConditionsOperation in experiment
15.6 g (35.6 mmol; 63%) With ammonium chloride;SiO2; In diethyl ether; dichloromethane; ethyl acetate; N,N-dimethyl-formamide; toluene; benzene; A. 3-(2-Phenyl-1H-indole-3-carbonyl)piperidine-1-carboxylic acid benzyl ester A solution of 14.8 g (56.3 mmol) of N-benzyloxycarbonylnipecotic acid in anhydrous dichloromethane (100 ml) under an atmosphere of nitrogen was treated with oxalyl chloride (7.4 ml, 84.4 mmol) followed by 2 drops of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 90 min at which time the dichloromethane was evaporated in vacuo. The residue was dissolved in anhydrous toluene (75 ml) and the resulting solution evaporated in vacuo. The residue was dissolved in anhydrous benzene (50 ml) to give Solution A. A solution of 21.7 g (113 mmol) of 2-phenylindole in anhydrous benzene (250 ml) under an atmosphere of nitrogen was added using a cannula to a solution of ethylmagnesium bromide (37.5 ml of a 3M solution in diethyl ether, 113 mmol) and the resulting mixture stirred at room temperature for 15 min to give Solution B. Solution A was added in one portion to rapidly stirred solution B and the resulting mixture stirred at room temperature for 30 min. The reaction was quenched by the addition of saturated ammonium chloride solution (200 ml). The organic layer was separated, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash chromatography (SiO2; 10% EtOAc in hexanes then 20% EtOAc in hexanes) to afford 15.6 g (35.6 mmol; 63%) of 3-(2-phenyl-1H-indole-3-carbonyl)piperidine-1-carboxylic acid benzyl ester as a clear oil. deltaH (360 MHz; CDCl3) 0.91-1.07 (1H, m, aliphatic), 1.50-1.65 (2H, m, aliphatics), 1.88-1.96 (1H, m, aliphatic), 2.58-2.82 (2H, m, aliphatics), 2.86-3.08 (1H, m, aliphatic), 3.92-4.06 (1H, m, aliphatic), 4.08-4.17 (1H, m, aliphatic), 5.05 (2H, d, J 3.8, PhCH2), 7.24-7.52 (13H, m, aromatics), 8.24-8.30 (1H, m, aromatic), 8.75 (1H, br s, NH); m/z (ES+) 439 (M++H, 100%).
  • 12
  • [ 851670-79-6 ]
  • [ 260-94-6 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • 13
  • [ 1075651-51-2 ]
  • [ 260-94-6 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • 14
  • [ 78385-26-9 ]
  • [ 948-65-2 ]
  • [ 1069473-27-3 ]
  • 15
  • [ 78385-26-9 ]
  • [ 948-65-2 ]
  • [ 1314235-54-5 ]
  • 16
  • [ 948-65-2 ]
  • [ 104-15-4 ]
  • [ 144657-66-9 ]
  • [ 1443528-02-6 ]
  • 18
  • [ 108-86-1 ]
  • [ 2727-71-1 ]
  • [ 536-74-3 ]
  • [ 948-65-2 ]
  • [ 3469-20-3 ]
  • 19
  • [ 948-65-2 ]
  • [ 57310-39-1 ]
  • 2-methylindolo[1,2-f]phenanthridine [ No CAS ]
  • 20
  • [ 948-65-2 ]
  • [ 97-08-5 ]
  • 3-(4-chloro-3-nitrophenylsulfinyl)-2-phenyl-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With zinc(II) oxide; In neat (no solvent); at 80℃; for 3h; General procedure: Indole (8.54 mmol), phenylsulfonyl chloride (10.25 mmol) and oxide fine powder (25.62 mmol) were blended and the mixture was stirred for the period indicated (TLC) at 80 C. After reaction, the crude mixture was washed with acetone or dichloromethane and filtered through celite. The concentrated filtrate was flash chromatographied (hexane/ethyl acetate 3/1, 5/1 or 1/3) on silica gel, obtaining the desired product. When indoles 1a, 1b, 1j and 1l andsulfonyl chlorides 2f, 2h, 2j, 2k were used, the correspondent 2- or 3-sulfinylindole 6 or 7 was also isolated.
  • 21
  • [ 221044-05-9 ]
  • [ 6843-66-9 ]
  • [ 948-65-2 ]
  • 22
  • [ 948-65-2 ]
  • [ 20651-67-6 ]
  • 1-(4-butylphenyl)-2-phenyl-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine; In toluene; at 110℃; for 24h;Inert atmosphere; General procedure: A 10 mL Schlenk tube was charged with 2-phenylindole 1a (193.2 mg, 1.0 mmol), CuI (10 mol%, 19.0 mg, 0.1 mmol) and K3PO4 (424 mg, 2.0 mmol). The Schlenk tube was evacuated and filled with N2 (this procedure was repeated three times), and then toluene (2.0 mL), DMEDA (20 mol%, 17.6 mg, 0.2 mmol) and iodobenzene 2a (244.8 mg, 1.2 mmol) were added. The resulting mixture was stirred at 110 C for 24 h. After cooling to room temperature, the reaction mixture was quenched and extracted with ethyl acetate (10 mL × 3). The organic extracts were combined, dried over Na2SO4 and concentrated under reduced pressure, and then purified by silica gel chromatograph (petroleum ether) to yield the desired product as a white solid (245.1 mg, 91% yield). The data of compounds 3a-q can be found in Supporting information.
  • 23
  • [ 948-65-2 ]
  • [ 80-17-1 ]
  • [ 3469-20-3 ]
  • 24
  • [ 948-65-2 ]
  • [ 399-25-7 ]
  • 2-(2-fluorophenyl)-2-(2-phenyl-1H-indol-3-yl)acetamide [ No CAS ]
  • 25
  • [ 948-65-2 ]
  • [ 110677-45-7 ]
  • 9-{4-[bis(2-phenyl-1H-indol-3-yl)methyl]phenyl}-9H-carbazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With hydrogenchloride; In tetrahydrofuran; methanol; at 20℃; for 2h; General procedure: 5-Methoxyindole (I) (1.42 g, 9.6 mmol) and concentrated hydrochloricacid (2 ml) were slowly added to tetrahydrofuran(1.1 ml) and methanol (11 ml) solution of <strong>[110677-45-7]4-(9H-carbazol-9-yl)benzaldehyde</strong> (1) (0.99 g, 3.6 mmol), and the mixture was stirredfor 2 h at room temperature. The resulting solutionwas poured intowater and filtered. The precipitate was dissolved in ethylacetateand washed with 10% NaOH solution. The separated organic layerwas dried over anhydrous Na2SO4. The crude product was purifiedby crystallization from diethyl ether to afford the product as brightyellow crystals.
  • 26
  • [ 948-65-2 ]
  • [ 1593-60-8 ]
  • [ 1213786-14-1 ]
  • 27
  • [ 948-65-2 ]
  • [ 456-14-4 ]
  • (1Z,3Z)-4-(4-fluorophenyl)-2-phenylbenzo[f][1,3,5]triazocin-6(5H)-one [ No CAS ]
  • 28
  • [ 948-65-2 ]
  • [ 57297-29-7 ]
  • (1Z,3Z)-4-cyclopropyl-2-phenylbenzo[f][1,3,5]triazocin-6(5H)-one [ No CAS ]
  • 29
  • [ 948-65-2 ]
  • [ 16799-05-6 ]
  • C22H14ClN [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With palladium diacetate; potassium hydroxide; tricyclohexylphosphine; In N,N-dimethyl-formamide; at 130℃; for 18h;Inert atmosphere; The reaction bottle by adding 0.5 millimoles of 2 - phenyl indole, 1.0 mmol 3 - chlorobenzene ethyl alkyne bromine, 3 mmol (6 equiv) potassium hydroxide, 5 muM % (0.025mmol) Pd (OAc)2, 15 muM % (0.075mmol) PCy3, 1.5 ml of N, N - dimethyl formamide, under nitrogen conditions, 130 C stirring for 18 hours, stop heating and stirring, cooled to the room temperature, distilled under reduced pressure to get the crude product, through the column chromatography separation and purification, to obtain the target product, the used column chromatography eluant is petroleum ether, yield 65%. This embodiment of the obtained product hydrogen spectrogram and carbon spectrogram as shown in Figure 11, Figure 12 is shown
  • 30
  • [ 948-65-2 ]
  • [ 456-14-4 ]
  • C21H14FN3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
78% With copper(I) oxide; oxygen; In 1-methyl-pyrrolidin-2-one; at 80℃; for 4h;Sealed tube; Green chemistry; 0.3 mmol of <strong>[456-14-4]4-fluorobenzamidine hydrochloride</strong> (No. 3 corresponding compound, 0.0579 g) was weighed out, 0.4 mmol of 2-phenyl-1-hydrogenindole (corresponding to (30) the corresponding compound, 0.0770 g) And 0.06 mmol cuprous oxide (0.0086 g) in 20 mL of the test tube reaction tube, Plus 3mL N-methyl pyrrolidone as solvent, tube mouth closed with oxygen balloon, Stirring at 80 ° C for 4 hours; after completion of the reaction, The reaction solution was extracted with ethyl acetate, dried over anhydrous sodium sulfate and separated by column chromatography (column chromatography separation conditions: the stationary phase was 300-400 mesh silica powder, the mobile phase was ethyl acetate (A) and petroleum ether (3) The mobile phase change procedure (A: B) was 1: 6) to give 0.0787 g of the reaction product. According to the characterization data, the reaction product was 2-phenyl-4- (4-fluorophenyl) -benzo [1,3,5] triazolidin-5-hydrogen-6-one (purity> 95percent); the product yield was calculated and the result was 78percent.
  • 31
  • [ 948-65-2 ]
  • [ 57297-29-7 ]
  • C18H15N3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% With copper(I) oxide; oxygen; In 1-methyl-pyrrolidin-2-one; at 80℃; for 4h;Sealed tube; Green chemistry; Weigh 0.3 mmol of cyclopropyl formamidine hydrochloride (corresponding to the compound (No. 13), 0.0363 g) 0.4 mmol of 2-phenyl-1-hydrogenindole (corresponding to (30) the corresponding compound, 0.0770 g) And 0.06 mmol cuprous oxide (0.0086 g) in 20 mL of the test tube reaction tube, Plus 3mL N-methyl pyrrolidone as solvent, tube mouth closed with oxygen balloon, Stirring at 80 ° C for 4 hours; after completion of the reaction, The reaction solution was extracted with ethyl acetate, dried over anhydrous sodium sulfate and separated by column chromatography (column chromatography separation conditions: the mobile phase was 300-400 mesh silica gel, the mobile phase was ethyl acetate (viii) and petroleum ether (3) The change procedure (A: B) was 1: 6) to obtain 0.0606 g of the reaction product. According to the data, we can see that the reaction product is pure 2-phenyl-4-cyclopropylbenzo [1,3,5] triazolidin-5-hydrogen-6-one (purity> 95percent); The product yield was calculated as a result of 72percent.
  • 32
  • [ 50-00-0 ]
  • [ 948-65-2 ]
  • [ 25365-71-3 ]
YieldReaction ConditionsOperation in experiment
78% With iron(III) chloride; ammonia; In water; N,N-dimethyl-formamide; at 130℃; for 2h; General procedure: A 50 mL round-bottomed flask equipped with a magnetic stirringbar was charged with the appropriate indole 1 (0.5 mmol,1.0 equiv), 37% aq HCHO (0.5 mmol, 0.0406 g, 1.0 equiv), 25% aqNH3 (1.0 mmol, 0.0681 g, 2.0 equiv), FeCl3 (0.01 mmol, 0.0016 g,2 mol%), and DMF (2 mL). The flask was fitted with a reflux condenser,and the mixture was stirred at 130 C under open air.When the reaction was complete (TLC), the mixture was cooledto r.t., diluted with sat. aq NaCl (10 mL) and 0.5 M aq HCl (2 mL),and extracted with EtOAc (3 x 7 mL). The organic layers werecombined, washed with sat. aq NaHCO3 (10 mL) and sat. aq NaCl(10 mL), dried (Na2SO4), and concentrated under reduced pressure.The residue was purified by flash column chromatography(silica gel, hexane-EtOAc).
  • 33
  • [ 948-65-2 ]
  • [ 298-12-4 ]
  • [ 25365-71-3 ]
  • 34
  • [ 948-65-2 ]
  • [ 399-25-7 ]
  • (3R*,4′S*)-4′-(2-fluorophenyl)-2-phenyl-4′H-spiro[indole-3,5′-isoxazole] [ No CAS ]
  • 35
  • [ 948-65-2 ]
  • [ 399-25-7 ]
  • 3-(1-(2-fluorophenyl)-2-nitroethyl)-2-phenyl-1H-indole [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% With acetic acid; In ethanol;Reflux; General procedure: A 5-mL round-bottom flask was charged with indole1(2.0 mmol), β-nitrostyrene2(2.1 mmol), acetic acid (10 μL) and ethanol (1 mL). The mixture was refluxed for 2-8 h, while the reaction progress was monitored by TLC. After complete consumption of the starting material, the mixture was cooled down to room temperature, and the resulting precipitate was collected by filtration. Alternatively, the reaction mixture was concentrated in vacuo, and the residue was purified by preparative column chromatography (eluent EtOAc/Hex 1:4).
With 2,2,2-trifluoroacetic acid ammonia; In ethanol; water;Reflux; General procedure: To a 100-mL round bottom flask containing 2-phenyl-1H-indole (1.0mmol, 1eq.), nitrovinyl building block (1.5mmol, 1.5eq.) and CF3COONH4 (0.5mmol) were dissolved with 10% aq. EtOH (10mL). The reaction mixture was refluxed at 105C for 12-18h. After reaction completion, the mixture was concentrated under reduced pressure to remove EtOH, diluted with ethyl acetate, then washed with water and brine. The aqueous phase was extracted 3X with ethyl acetate, and the combined organic extracts were dried with Na2SO4 then concentrated under reduced pressure. The crude organic resin was purified by silica gel flash chromatography using ethyl acetate/hexanes eluent to obtain the desired conjugate product.
 

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