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Structure of 3652-89-9

Chemical Structure| 3652-89-9

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Product Details of [ 3652-89-9 ]

CAS No. :3652-89-9
Formula : C12H8BrN
M.W : 246.10
SMILES Code : BrC1=CC=CC(N2)=C1C3=C2C=CC=C3
MDL No. :MFCD18450175
InChI Key :CBJHFGQCHKNNJY-UHFFFAOYSA-N
Pubchem ID :58338270

Safety of [ 3652-89-9 ]

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

Computational Chemistry of [ 3652-89-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 13
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 63.5
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.

2.14
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

4.56
Log Po/w (WLOGP)?

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

4.08
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.

3.5
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

4.25
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.71

Water Solubility

Log S (ESOL):?

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

-4.93
Solubility 0.00292 mg/ml ; 0.0000119 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-4.61
Solubility 0.00598 mg/ml ; 0.0000243 mol/l
Class?

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

Moderately 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

-5.82
Solubility 0.000375 mg/ml ; 0.00000152 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

Yes
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.

-4.56 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<2.0
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)

1.61

Application In Synthesis of [ 3652-89-9 ]

* 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 [ 3652-89-9 ]

[ 3652-89-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 108-86-1 ]
  • [ 3652-89-9 ]
  • [ 1097884-37-1 ]
YieldReaction ConditionsOperation in experiment
82% With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 110℃; Add 31.4g of bromobenzene and 54.1g of 4-bromo-9H-carbazole to a dry 2L three-necked flask. Dry and degassed 600 mL of toluene was added as a solvent. Add 57.7g of sodium tert-butoxide, 0.9g catalyst palladium acetate (2% mol) and 5.0g ligand 1,1'- Binaphthyl-2,2'-bisdiphenylphosphine (BINAP, 4% mol). The temperature was raised to 110C and the reaction ended overnight. Cool to room temperature Add activated carbon adsorption, suction filtration, remove solvent, Recrystallization from toluene and ethanol gave 52.8 g of Intermediate Q (yield 82%).
79% With 18-crown-6 ether; copper; potassium carbonate; In water; for 10h;Reflux; 4-Bromo-9H-carbazole (6 g, 24.38 mmol), copper powder (3.09 g, 48.76 mmol) and 18-crown-6 (0.65 g, 2.44 mmol) were dissolved in bromobenzene (60 ml) followed by addition of K2CO3 (8.29 g, 2 M) in water (30 ml). The mixture was refluxed for 10 h and cooled to room temperature and extracted with methylene chloride and water. The combined organic layer was dried over MgSO4 and concentrated. Purification by column chromatography using n-hexane gave a white form. The product was obtained to 6.2 g(yield 79%). 1H NMR (200 MHz, CDCl3): δ 8.84 (d, 1H, J = 8.0 Hz), 7.66-7.19(m, 11H). MS (FAB) m/z 323[(M + H)+].
77% With dibenzo-18-crown-6; potassium acetate; copper; In N,N-dimethyl-formamide; at 120℃; for 4h; Intermediate 2-1 (2.1 g, 0.010 mol) in bromobenzene (1.6 g, 0.010 mol), dibenzo-18-crown-6 (1.1 g, 0.0030 mol), copper (2) (1.2 g, 0.020 mol), potassium acetate Insertthe DMF to 100 mL (2.8 g, 0.020 mol) was reacted with stirring for 4 hours at 120 C.After layer separation the MC column purification (n-Hexane:: MC) After completion ofthe reaction by cooling to H20 to afford 2.3 g of Intermediate 2-2 (yield 77%)
77% With dibenzo-18-crown-6; potassium acetate; copper; In N,N-dimethyl-formamide; at 120℃; for 4h; General procedure: 2-aminobenzamide (1.4g, 0.010mol) in dibromochloromethane (2.1g, 0.010mol) dibenzo-18-crown-6 (1.1g, 0.0030mol), copper (2) (1.2g, 0.020mol), potassium acetate (2.8 g, 0.020mol), into a DMF in 100ml was reacted with stirring for 4 hours at 120 C. After the reaction cooled to H20: After layer separation the MC column purification (n-Hexane: MC) to yield the intermediate 1-1 1.1g (62% yield). Intermediate 1-8 (2.1g, 0.010mol) put in bromobenzene (1.6g, 0.010mol), by synthesis by the same method used in preparation Example 1-1 to give <Intermediate 1-9> 2.3g (yield 77%).

  • 2
  • [ 3652-89-9 ]
  • [ 591-50-4 ]
  • [ 1097884-37-1 ]
YieldReaction ConditionsOperation in experiment
97% With copper(l) iodide; potassium carbonate; 1-(2-pyridyl)-3-(2-pyridyl)-1,3-propanedione; In N,N-dimethyl-formamide; at 110℃;Inert atmosphere; A 500 ml four-neck flask is initially charged with 15.0 g (61.0 mmol, 1.0 eq) of 4-bromo-9H-carbazole 1a (CAS 3652-89-9) together with 13.6 ml (122 mmol, 2.0 eq) of iodobenzene 2a and 16.8 g (122 mmol, 2.0 eq) of potassium carbonate, which are dissolved in 180 ml of dried DMF. After degassing by means of a nitrogen stream for 30 minutes, 1.38 g (6.10 mmol, 0.10 eq) of 1,3-di(2-pyridyl)-1,3-propanedione and 1.16 g (6.10 mmol, 0.10 eq) of copper(I) iodide are added. The mixture is stirred at 110 C. overnight and, after the reaction has ended, the solvent is removed on a rotary evaporator. The residue is taken up in 250 ml of DCM, conc. ammonium chloride solution is added and the mixture is filtered through Celite. Subsequently, the phases are separated, the aqueous phase is extracted twice with 100 ml each time of DCM and the combined organic phases are finally washed with water. After drying over sodium sulphate and removing the solvent under reduced pressure, the oily residue together with heptane is filtered through silica gel and the solvent is again removed on a rotary evaporator. 19.0 g(59.0 mmol, 97%) of a colourless oil 3a are obtained.
95% With dibenzo-18-crown-6; copper; potassium carbonate; at 150℃; for 24h; Intermediate 1-2 (1 g, 0.0041 mol) iodo benzene (2.1 g, 0.0102 mol / sigma Aldrich) potassium carbonate (2.2 g, 0.0163 mol), dibenzo-18-crown-6 (0.1 g, 0.0004 mol / sigma Aldrich) , 30 ml of bromobenzene was added to Copper (0.5 g, 0.0081 mol / sigma aldrich) and stirred at 150 C. for 24 hours for reaction. After the completion of the reaction, the mixture was cooled and separated by H20: MC, followed by column purification (n-Hexane: MC) to obtain 1.3g of intermediate 1-3 (yield 95%).
92% With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene; at 140℃; for 16h;Sealed tube; 4-bromo-9H-carbazole (4-bromo-9H-carbazole) 50g (203.16mmol), iodo- benzene (Iodobenzene) 68mL (609.48mmol), Cu1.3g (20.32mmol), K2CO3 56g (406.32mmol) , 18-crown-6-ether (18-crown-6-ether) 6.6g (20.32mmol) 1,2-dichlorobenzene (1,2-dichlorobenzene) 140C with 1L, in a sealed tube (sealed tube) It was reacted for 16 hours. After the reaction was complete, after cooling to room temperature and extracted with distilled water and dichloromethane (dichloromethane). The organic layer was dried over anhydrous MgSO4After removing the solvent on a rotary evaporator then it was purified by column chromatography using dichloromethane and hexane as a developing solvent to obtain the title compound A-1 60.0g (92%).
89% With 1,10-Phenanthroline; 18-crown-6 ether; potassium carbonate; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 180℃;Inert atmosphere; Under nitrogen protection, 4-bromocarbazole (20g, 81.3mmol),Iodobenzene (99.5g, 487.6mmol),Cuprous chloride (4.0g, 40.6mmol),Potassium carbonate (168.5g, 1218.9mmol), 18-crown-6 (10.7g, 40.6mmol),1,10-Phenanthroline (7.3g, 40.6mmol) and N-methylpyrrolidone (508mL) were added to a three-necked flask and reacted at 180 C overnight. After cooling to room temperature, distilled water was added, the mixture was extracted with dichloromethane, the organic phase was washed with water, the organic phase was dried over anhydrous sodium sulfate and concentrated to remove the solvent, and the residue was purified by column chromatography (pure petroleum ether) to give beige oily intermediate B 116g (yield: 89%).
88% With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene; at 180℃; for 24h; 4-bromo-9H-carbazole 20.0 g (81.3 mmol), 2-iodobenzene 33.2 g (162.5 mmol), copper powder 10.3 g (162.5 mmol), 18-crown-6 4.3 g (16.3 mmol), 33.7 g (243.9 mmol) of potassium carbonate was added in order, 200 ml of 1,2-dichlorobenzene was added, and the mixture was refluxed and stirred at 180 C. for 1 day. When the reaction was completed, the solution was concentrated under reduced pressure after a high temperature filter, and the organic layer solution was subjected to column chromatography with hexane to obtain 21.0 g of [Intermediate 1-e]. (Yield 88%)
88% With 18-crown-6 ether; copper; potassium carbonate; In 1,2-dichloro-benzene; at 180℃; for 24h; 4-bromo-9H-carbazole 20.0 g (81.3 mmol), 2-iodobenzene 33.2 g (162.5 mmol),Copper powder 10.3 g (162.5 mmol), 18-crown-6 4.3 g (16.3 mmol), potassium carbonate 33.7 g (243.9 mmol) were added in order,After adding 200 ml of 1,2-dichlorobenzene, the mixture was refluxed and stirred at 180 C. for 1 day.When the reaction was completed, the solution was concentrated under reduced pressure after high-temperature filtering, and the organic layer solution was subjected to column chromatography with hexane to obtain 21.0 g of [Intermediate 5-b]. (Yield 88%)
83% With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Inert atmosphere; Reflux; A 5 L flask was charged with 200.0 g (0.8 mol) of intermediate 4-bromo-9H-carbazole,248.7 g (1.2 mol) of iodobenzene,168.5 g (1.2 mol) of potassium carbonate,31.0 g (0.2 mol) of copper iodide (CuI) 29.3 g (0.2 mol) of 1,10-phenanthroline was added to 2.5 L of N, N-dimethylformamide,And refluxed under a nitrogen stream for 24 hours.The resulting mixture was added to 4 L of distilled water, and the crystallized solid was filtered, washed with water, methanol and hexane. The obtained solid was extracted with water and dichloromethane, and the obtained water was removed from the obtained organic layer using magnesium sulfate. The filtrate was concentrated and purified by column chromatography to obtain Intermediate C-1 as a white solid (216.2 g, 83% yield) .
83% With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Reflux; Inert atmosphere; In a 5 L flask, Bromo-9H-carbazole 200.0 g (0.8 mol),248.7 g (1.2 mol) of iodobenzene,168.5 g (1.2 mol) of potassium carbonate,31.0 g (0.2 mol) of copper (I) iodide,29.3 g (0.2 mol) of 1,10-phenanthrolineAfter adding 2.5 L of N, N-dimethylformamide,And refluxed under a nitrogen stream for 24 hours.The resulting mixture was added to 4 L of distilled water, and the crystallized solid was filtered, washed with water, methanol and hexane.The obtained solid was extracted with water and dichloromethane, and water was removed from the obtained organic layer using magnesium sulfate and concentrated,Purification by column chromatography gave Intermediate C-1 as a white solid(216.2 g, 83% yield).
83% With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Inert atmosphere; Reflux; A 5 L flask was charged with 200.0 g (0.8 mol) of intermediate 4-bromo-9H-carbazole, 248.7 g (1.2 mol) of iodobenzene, 168.5 g (1.2 mol) of potassium carbonate, 31.0 g (0.2 mol) of copper (I) iodide and 29.3 g (0.2 mol) of 1,10-phenanthroline were added to 2.5 L of N, N-dimethylformamide, And refluxed under a nitrogen stream for 24 hours. The resulting mixture was added to 4 L of distilled water and the crystallized solid was filtered, Water and methanol,Washed with hexane. The obtained solid was extracted with water and dichloromethane, and the obtained aqueous layer was extracted with magnesium sulfate. The filtrate was concentrated and purified by column chromatography to obtain Intermediate I-1 as a white solid (216.2 g, 83% yield) .
83% With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Inert atmosphere; Reflux; A 5 L flask was charged with 200.0 g (0.8 mol) of intermediate 4-bromo-9H-carbazole,248.7 g (1.2 mol) of iodobenzene,168.5 g (1.2 mol) of potassium carbonate,31.0 g (0.2 mol) of copper (I) iodide,29.3 g (0.2 mol) of 1,10-phenanthroline,Was added to 2.5 L of N, N-dimethylformamide,And refluxed under a nitrogen stream for 24 hours.The resulting mixture was added to 4 L of distilled water, and the crystallized solid was filtered, washed with water, methanol and hexane. The obtained solid was extracted with water and dichloromethane, and the obtained aqueous layer was extracted with magnesium sulfate. The filtrate was concentrated and purified by column chromatography to obtain Intermediate I-1 as a white solid (216.2 g, 83% yield) .
83% With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; for 24h;Reflux; Inert atmosphere; 200.0 g (0.8 mol) of an intermediate of 4-bromo-9H-carbazole, 248.7 g (1.2 mol) of iodo benzene, 168.5 g (1.2 mol) of potassium carbonate, 31.0 g (0.2 mol) of copper(I) iodide, and 29.3 g (0.2 mol) of 1,10-phenanthroline were mixed with 2.5 L of N,N-dimethylformamide in a 5 L flask, and the mixture was refluxed under a nitrogen flow for 24 hours. The obtained mixture was added to 4 L of distilled water, and a solid crystallized therein was filtered and washed with water, methanol, and hexane. Subsequently, the solid was extracted with water and dichloromethane, and an organic layer obtained therefrom was treated by using magnesium sulfate to remove moisture and then, concentrated and purified through column chromatography to obtain Intermediate I-1 as a white solid (216.2 g, a yield of 83%).
81% With copper(l) iodide; 1,10-Phenanthroline; potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 24h;Inert atmosphere; [287] In a 100 ml round-bottom three-neck flask under a nitrogen atmosphere, 2.6 g of Intermediate 24, 2.6 g of iodobenzene, 0.2 g of copper iodide, 0.2 g of1, 10-phenanthroline, 4.4 g of potassium carbonate and 30 ml of dimethylfomiamide were placed, and reacted at 80C for 24 hrs. The reaction solution was cooled and then extracted with dichloromethane and water. The extracted solution was concentrated, subjected to column chromatography using a solvent mixture of dichloromethane and n-hexane and then concentrated, thus obtaining 2.7 g of Intermediate 25 (yield 8 1%).[288] MS (ESI): [M+Hj 322
75% With tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; sodium t-butanolate; In toluene; at 100℃; Reaction is progressed in 100C after putting the sub 6-4-4 (4.9g, 20mmol), sub 6-4-5 (4.1g, 20mmol), pd2(dba)3 (0.9g, 1 mmol), PPh3 (0.5g, 2mmol), NaOt-Bu (5.8g, 60mmol), toluene (210mL) in the round bottom flask. If reaction was completed the organic compound which was dry to the MgSO4 and was the organic layer generated after doing the concentration was re-determined as ether and water after doing the extraction with the silicagel column and the Sub 6-4-6 was obtained with 4.8g (yield : 75%).
75% With tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; sodium t-butanolate; In toluene; at 100℃; To a round bottom flask Sub 1-1-4-1 (4.9g, 20mmol), Sub 1-1-5-1 (4.1g, 20mmol), Pd2 (dba) 3 (0.9g, 1mmol), PPh3 (0.5g , 2mmol), and NaOt-Bu (5.8g, 60mmol), the reaction proceeds at 100 C after loading into toluene (210mL). After the reaction was completed, the organic layer was dried over MgSO4 and the ether was extracted with water and the resulting organics concentrated to silica gel column and recrystallized the Sub 1-1-6-1 4.8g (yield: 75%) was obtained.
73% With 18-crown-6 ether; copper; potassium carbonate; In N,N-dimethyl-formamide; at 190℃; for 12h;Inert atmosphere; A 1000 mL 2-neck round bottom flask was charged with intermediate 6-2 (100.0 mmol, 24.6 g), Iodobenzene (120.0 mmol, 24.5 g),Cu-metal (110.0 mmol, 7.0 g), K2CO3 (150.0 mmol, 20.7 g),18-Crown-6 (10.0 mmol, 2.64 g) was charged and charged with nitrogen. 500 mL of dimethylformamide was added as a solvent, and the mixture was refluxed at 190 DEG C for 12 hours.The temperature of the reaction solution was lowered to room temperature and extracted with water and diethyl ether. The obtained extract was dried over MgSO4 and dried under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography to obtain 23.5 g (yield: 73%) of Intermediate 6-3 as a yellow solid.
68% 4-bromo-9Hcarbazole(2 g, 8 mmol), copper(Ι) iodide (1.24 g, 6.5 mmol), cesiumcarbonate (7.98 g, 24 mmol) were added to 25 mL of anhydrous toluenesolution in 3-neck round bottom flask under N2 atmosphere. After themixture was heated at 80 C, iodobenzene (1.82 mL, 16 mmol), ethylenediamine(0.82 mL, 12.2 mmol) was added to mixture. Then themixture was refluxed at 110 C for 15 h (1.7 g, Yield 68%) 1H NMR(300 MHz, THF): δ(ppm) 8.81-8.78 (d, 1H), 7.65-7.59 (t, 2H),7.56-7.47 (m, 3H), 7.45-7.40 (m, 2H), 7.35-7.27 (q, 3H), 7.25-7.20 (t,1H).
With tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; sodium t-butanolate; In toluene; at 100℃; for 24h; 2-bromo-9H-carbazole ( 327mmol) and iodobenzene (360mmol), toluene (2800mL) Pd2(dba) 3 (8.24g, 9mmol), PPh3 (7.87g, 30mmol), NaOt-Bu ( 86.5g, 900mmol) were added to each, and refluxed under stirring for 24 hours at 100 C. ether and extracted with water and the organic layer is MgSO 4 and then dried, and concentrated to the resulting organic silicagel column and recrystallization to give the 2-bromo-9-phenyl- 9H-carbazole.
With 18-crown-6 ether; copper; potassium carbonate; In N,N-dimethyl-formamide; at 190℃; for 12h;Inert atmosphere; A 1000 mL 2-neck round bottom flask was charged with intermediate 6-2 (100.0 mmol, 24.6 g), Iodobenzene (120.0 mmol, 24.5 g), Cu metal (110.0 mmol, 7.0 g), K2CO3 (150.0 mmol, 20.7 g), 18-Crown-6 (10.0 mmol, 2.64 g) was charged and charged with nitrogen. To this was added 500 mL of dimethylformamide as a solvent And then refluxed at 190 C for 12 hours. The temperature of the reaction solution was lowered to room temperature and extracted with water and diethyl ether. The obtained extract was dried over MgSO4 and dried under reduced pressure to obtain a crude product. The crude product was separated and purified by silica gel column chromatography to obtain 23.5 g (yield: 73%) of Intermediate 6-3 as a yellow solid

  • 3
  • [ 3652-89-9 ]
  • [ 100-63-0 ]
  • [ 1097884-37-1 ]
YieldReaction ConditionsOperation in experiment
95% With copper(l) iodide; caesium carbonate; In acetonitrile; at 0℃; for 4h;Schlenk technique; Add 0.6mmol (65mg) of substrate phenylhydrazine, 0.2mmol (50mg) of 4-bromocarbazole, 2mg (5mol%) of cuprous iodide, 130mg (4eq.) of cesium carbonate, 2mL of acetonitrile to a 50mL Schlenk tube. Magnet, stirring at 0C for 4h. After the reaction is over, add 50 mL of saturated brine, extract three times with 3*50 mL of dichloromethane, add anhydrous sodium sulfate to dry for 30 minutes, and then use a rotary evaporator to remove the low-boiling solvent. The reaction liquid was subjected to column evaporation after rotary evaporation to obtain the target product with a yield of 95%.
 

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