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Chemical Structure| 2106-50-5 Chemical Structure| 2106-50-5

Structure of 2106-50-5

Chemical Structure| 2106-50-5

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Product Details of [ 2106-50-5 ]

CAS No. :2106-50-5
Formula : C6H3ClFNO2
M.W : 175.55
SMILES Code : C1=C(C(=CC(=C1)F)Cl)[N+]([O-])=O
MDL No. :MFCD03412200
InChI Key :KQOOFMWRLDRDAX-UHFFFAOYSA-N
Pubchem ID :75017

Safety of [ 2106-50-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 2106-50-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 40.23
TPSA ?

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

45.82 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.42
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

2.54
Log Po/w (WLOGP)?

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

2.81
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.

1.9
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

0.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.89

Water Solubility

Log S (ESOL):?

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

-2.87
Solubility 0.239 mg/ml ; 0.00136 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.

-3.15
Solubility 0.125 mg/ml ; 0.000709 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

-2.67
Solubility 0.375 mg/ml ; 0.00214 mol/l
Class?

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

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.57 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

2.0 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)

1.81

Application In Synthesis of [ 2106-50-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 2106-50-5 ]

[ 2106-50-5 ] Synthesis Path-Downstream   1~54

  • 2
  • [ 2106-50-5 ]
  • [ 35852-58-5 ]
  • [ 42874-16-8 ]
  • 3
  • [ 625-98-9 ]
  • [ 2106-50-5 ]
YieldReaction ConditionsOperation in experiment
16.7% With sulfuric acid; nitric acid; In hexane; benzene; (a) 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) ae added. The extract is washed with water (1+300 ml.), sodium carbonate solution (1*300 ml.), and water (1*300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C.
16.7% With sulfuric acid; nitric acid; In hexane; benzene; a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1*300 ml.), are added. The extract is washed with water (1*300 ml.), sodium carbonate solution (1*300 ml.), and water (1*300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C.
16.7% With sulfuric acid; nitric acid; In hexane; benzene; (a) 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1*300 ml.), sodium carbonate solution (1*300 ml.), and water (1*300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C.
16.7% With sulfuric acid; nitric acid; In hexane; benzene; a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1 * 300 ml.), sodium carbonate solution (1 * 300 ml.), and water (1 * 300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C.
16.7% With sulfuric acid; nitric acid; In hexane; benzene; a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1 * 300 ml.), are added. The extract is washed with water (1 * 300 ml.), sodium carbonate solution (1 * 300 ml.), and water (1 * 300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitro-fluorobenzene (51 g. 16.7%) m.p. 36-38 C.
16.7% With sulfuric acid; nitric acid; In hexane; benzene; a. 3-Chloro-4-nitrofluorobenzene m-Chlorofluorobenzene (240 g. 1.85 moles) is added to a mixture of sulfuric acid (185 g. 1.85 moles) and nitric acid (166 g., 1.85 moles) at -5 C. in 3.5 hours, stirred 13 hours, then benzene (200 ml.) and hexane (200 ml.) are added. The extract is washed with water (1 * 300 ml.), sodium carbonate solution (1 * 300 ml.), and water (1 * 300 ml.), dried and the solvents removed. The residue is distilled to give 138 g. of mixed isomers. The 4-nitro isomer crystallizes and is filtered off to give 3-chloro-4-nitrofluorobenzene (51 g. 16.7%) m.p. 36-38 C.
With sodium nitrate; methanesulfonic acid; at 20 - 30℃; A 500 mL flask was charged with commercially available 1-chloro-3-fluorobenzene (20.0 g, 0.153 mol) and methane sulfonic acid (100 mL). The reaction was vigorously stirred and sodium nitrate (13.0 g, 0.153 mol) was added in small portions to the reaction mixture while the temperature was maintained below 30 C. using a water bath for external cooling. After addition of sodium nitrate the reaction was stirred at RT for 4 hours. The reaction mixture was poured into 500 mL ice-water and the aqueous layer was extracted with dichloromethane (3×250 mL). The organic extracts were washed once with saturated NaHCO3/H2O (500 mL). The combined extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was distilled (bp 71 C., 2.3 torr) to obtain 2-chloro-4-fluoronitrobenzene as a clear oil (14.6 g, 54%, purity (GC)=84%).

  • 4
  • [ 2106-50-5 ]
  • [ 2369-11-1 ]
  • 5
  • [ 2106-50-5 ]
  • [ 109-73-9 ]
  • [ 951666-45-8 ]
  • 6
  • [ 611-06-3 ]
  • [ 2106-50-5 ]
  • [ 446-35-5 ]
  • [ 700-37-8 ]
  • 7
  • [ 2106-50-5 ]
  • [ 5763-61-1 ]
  • [ 1026026-68-5 ]
  • 9
  • [ 2106-50-5 ]
  • [ 609-08-5 ]
  • [ 26039-74-7 ]
  • 10
  • [ 131112-05-5 ]
  • [ 2106-50-5 ]
  • 3',4'-dichloro-2-nitro-5-fluorobiphenyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% With sodium hydroxide;triphenylphosphine; palladium dichloride; In 1,4-dioxane; water; at 85℃; for 6h; Example 3: Reaction of di(3,4-dichlorophenyl)borinic acid and 2-chloro-4-fluoro-1 - nitro-benzen; A reaction flask is initially charged with 0.55 g of sodium hydroxide (13.7 mM) and 50 mL of water at 15-200C.To this are metered 2,5 g of di(3,4-dichlorophenyl)borinic acid (7.8 mM) and 0.199 g of triphenylphosphine (0.76 mM) in 50 mL of dioxane. After full addition, the reaction solution is stirred at 18-22C for 40 minutes. After deoxygenation, 27 mg of palladium(ll) chloride (0.15 mM) and 1 ,3 g of 2-chloro-4-fluoro-1 -nitro-benzene (7.4 mM) are added to the reaction solution. The reaction solution is heated to 85C for 6 hours.The reaction mixture is cooled down, acidified with 2 M hydrochloric acid and the dioxane evaporated. The residue is extracted with dichloromethane and after evaporation of solvent the 3',4'-dichloro-5-fluoro-2-nitro-biphenyl is isolated by column chromatography (0.76 g, yield 36%). GC-MS: m/z = 285.9 [m-H]-
  • 11
  • [ 2106-50-5 ]
  • 2-(3-chloro-4-iodo-phenyl)-propionic acid [ No CAS ]
  • 12
  • [ 2106-50-5 ]
  • 2-(3-chloro-4-iodo-phenyl)-2-methyl-malonic acid diethyl ester [ No CAS ]
  • 13
  • [ 2106-50-5 ]
  • 2-(2-chloro-4'-trifluoromethyl-biphenyl-4-yl)-propionic acid [ No CAS ]
  • 14
  • [ 2106-50-5 ]
  • [ 25814-36-2 ]
  • 15
  • [ 2106-50-5 ]
  • [ 1026954-54-0 ]
  • 16
  • [ 2106-50-5 ]
  • [ 180207-99-2 ]
  • 17
  • [ 2106-50-5 ]
  • [ 1026407-10-2 ]
  • 18
  • [ 2106-50-5 ]
  • 7-fluoro-3-(4-fluorophenyl)-4,5-dihydro-5-[(morpholino)carbonyl]imidazo[1,5-a]quinoxaline [ No CAS ]
  • 19
  • [ 2106-50-5 ]
  • [ 148891-12-7 ]
  • 20
  • [ 2106-50-5 ]
  • [7-Fluoro-3-(4-fluoro-phenyl)-4H-imidazo[1,5-a]quinoxalin-5-yl]-(3,4,5-trimethyl-piperazin-1-yl)-methanone [ No CAS ]
  • 21
  • [ 2106-50-5 ]
  • [ 1026071-37-3 ]
  • 22
  • [ 2106-50-5 ]
  • [ 1026965-28-5 ]
  • 23
  • [ 2106-50-5 ]
  • [ 1026963-18-7 ]
  • 24
  • [ 2106-50-5 ]
  • N2-Butyl-4-fluoro-benzene-1,2-diamine [ No CAS ]
  • 25
  • [ 2106-50-5 ]
  • 1-Butyl-2-chloro-6-fluoro-1H-benzoimidazole [ No CAS ]
  • 26
  • [ 2106-50-5 ]
  • 1-Butyl-6-fluoro-1,3-dihydro-benzoimidazol-2-one [ No CAS ]
  • 27
  • [ 2106-50-5 ]
  • 1-Butyl-6-fluoro-2-(4-methyl-piperazin-1-yl)-1H-benzoimidazole [ No CAS ]
  • 28
  • [ 2106-50-5 ]
  • [ 131885-90-0 ]
  • 29
  • [ 2106-50-5 ]
  • [ 131886-10-7 ]
  • 30
  • [ 2106-50-5 ]
  • [ 131885-76-2 ]
  • 31
  • [ 2106-50-5 ]
  • [ 131885-66-0 ]
  • 32
  • [ 2106-50-5 ]
  • 2-Pyridin-4-yl-5-[1,2,4]triazol-1-yl-1H-benzoimidazole [ No CAS ]
  • 33
  • [ 2106-50-5 ]
  • 2'-Pyridin-4-yl-1'H-[1,5']bibenzoimidazolyl [ No CAS ]
  • 34
  • [ 2106-50-5 ]
  • [ 2812-46-6 ]
  • [ 230642-97-4 ]
YieldReaction ConditionsOperation in experiment
90% With N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 110℃; for 48h; To a solution of L-proline tert-butyl ester (1.06 g, 7.5 mmol) in dry DMSO (10 ml) were added <strong>[2106-50-5]3-chloro-4-nitrofluorobenzene</strong> (1.48 g, 8.4 mmol) and diisopropylethylamine (2.60 mL, 15 mmol). The resulting solution was heated at 110 C. in a sealed tube for 48 hours. The reaction mixture was cooled to room temperature and partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water, dried over sodium sulfate, and concentrated in vacuo. Purification of the crude residue on silica gel (7:3/EtOAc-hexanes) provided 1.98 g (90%) of a pale yellow solid. 1H NMR (CD3OD) delta 8.13 (1H, d, J=2.7 Hz), 8.02 (1H, dd, J=9.3 Hz, 2.7 Hz), 6.92 (1H, d, J=9.3 Hz), 5.01 (1H, dd, J=9.2 Hz, 3.9 Hz), 3.35 (1H, m), 3.30 (1H, m), 2.31 (1H, m), 2.07 (1H, m), 2.02 (2H, m), 1.38 (9H, s).
1.98 g (90%) In dimethyl sulfoxide; A. (S)-1-(3-Chloro-4-nitrophenyl)-2-pyrrolidinecarboxylic acid 1,1-dimethylethyl ester STR330 To a solution of L-proline tert-butyl ester STR331 (1.06 g, 7.5 mmol) in dry DMSO (10 ml) were added <strong>[2106-50-5]3-chloro-4-nitrofluorobenzene</strong> (1.48 g, 8.4 mmol) and duisopropylethylamine (2.60 mL, 15 mmol). The resulting solution was heated at 110 C. in a sealed tube for 48 hours. The reaction mixture was cooled to room temperature and partitioned between brine and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water, dried over sodium sulfate, and concentrated in vacuo. Purification of the crude residue on silica gel (7:3/EtOAc-hexanes) provided 1.98 g (90%) of a pale yellow solid. 1 H NMR (CD3 OD): d 8.13 (1H, d, J=2.7 Hz), 8.02 (1H, dd, J=9.3 Hz, 2.7 Hz), 6.92 (1H, d, J=9.3 Hz), 5.01 (1H, dd, J=9.2 Hz, 3.9 Hz), 3.35 (1H, m), 3.30 (1H, m), 2.31 (1H, m), 2.07 (1H, m), 2.02 (2H, m), 1.38 (9H, s).
  • 35
  • potassium salt of 5-methyl salicylaldehyde [ No CAS ]
  • [ 2106-50-5 ]
  • 2-(2-nitro-4-fluorophenoxy)-5-methylbenzaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
In water; EXAMPLE 15 200 Parts of <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> is heated to 160 C. and stirred and 160 parts of the potassium salt of 5-methyl salicylaldehyde is added over a 30 minute period. After an exothermic reaction the mixture is heated at 150 C. for 1 hour. The mixture is cooled, ice and water are added, and it is then extracted with ether. The ether is filtered to remove insoluble material and the resultant solution is dried over sodium sulfate. The ether solvent is then evaporated and the residual oil is recrystallized from a mixture of hexane and benzene to provide 2-(2-nitro-4-fluorophenoxy)-5-methylbenzaldehyde having the following structural formula STR27 A solution of 55 parts of this material is placed in 800 parts of ethanol and hydrogenated over Raney nickel catalyst at room temperature and atmospheric pressure.
  • 36
  • [ 5308-25-8 ]
  • [ 2106-50-5 ]
  • [ 943189-54-6 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 6h; 1-(3-Chloro-4-nitro-phenyl)-4-ethyl-piperazineN-Ethylpiperazine (4.3 mL, 34.3 mmol, 1.2 equiv) is added to a mixture of 2-chloro-4- fluoronitrobenzene (5 g, 28.6 mmol) and potassium carbonate (7.9 g, 57.1 mmol, 2 equiv) in DMF (50 mL). The reaction mixture is stirred at 1000C for 6h, allowed to cool to RT1 diluted with H2O and extracted with EtOAc. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. The residue is purified by trituration in diethyl ether to provide 5.6 g of the title compound as a yellow solid: ES-MS: 270.0 [MH]+; tR= 2.90 min (system 1).
  • 37
  • [ 2106-50-5 ]
  • [ 23244-88-4 ]
  • [ 1056619-65-8 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 6h; Example 211; Synthesis of [6-(lH-indazol-6-yloxy)-lH-benzimidazol-2-yl]-(2-trifluoromethylphenyl)- amineTo a stirred suspension of 6-aminoindazole (20 mmol) in concentrated HCl (6 mL) at 00C was added a solution of NaNtheta2 (22 mmol) in water (12 mL) in portions. During the addition, the temperature of the reaction mixture was maintained at 0-5 0C, and the stirring continued for additional 45 min. The contents were then added into a flask containing 1 % aqueous HCl (200 mL), and heated at 1000C. The reaction mixture was then stirred at 100 0C for 5 h. The contents were cooled to RT, neutralized to pH 7 using 5% aqueous Na2COs, and extracted with EtOAc (2x70 mL). Combined organic layers were washed with brine and dried over anhydrous Na2SO4. Removal of solvent under vacuum provided 6- hydroxyindazole as dark brown solid, which was used for further transformation without any purification.To a stirred solution of 2-chloro-4-fluoro-l -nitrobenzene (3 mmol) in DMF (5 mL) was added 6-hydroxyindazole (3 mmol) and K2CO3 (6 mmol). The contents were heated at900C for 6 h. The reaction mixture was cooled to RT, and the contents were poured onto ice cold water with vigorous stirring. The solid formed was collected by filtration, washed with water, and dried in vacuo to provide the product, 6-(3-chloro-4-nitrophenoxy)-lH-indazole as a yellow solid, which was used for further transformation without any purification. A stirred solution of the nitro compound (2 mmol) in DMF (4 mL) was added with benzylamine (4 mmol) and contents were heated at 100 0C for 6 h. The reaction mixture was cooled to RT and the contents were poured onto ice cold water with vigorous stirring. The solid formed was collected by filtration, washed with water, and dried in vacuo. The residue obtained was purified on silica gel column chromatography using hexane/EtOAC as eluent to provide the product, benzyl-[5-(lH-indazol-6-yloxy)-2-nitrophenyl]-amine as a yellow solid. <n="111"/>The nitroaniline (1 mmol) obtained as above was reduced under hydrogenation conditions as described in general procedure F to 4-(l H-Indazol-6-yloxy)-benzene-l,2- diamine.The diamine (0.3 mmol) from above was reacted with l-isothiocyanato-2- trifluoromethylbenzene (0.3 mmol) followed by cyclization in situ using EDC as described in general procedure B to provide [6-(lH-indazol-6-yloxy)-lH-benzimidazol-2-yl]-(2- trifluorornethylphenyl)-arnine. MS: m/? 40 (M+H)+.
  • 38
  • [ 53779-90-1 ]
  • [ 2106-50-5 ]
  • [ 748182-89-0 ]
YieldReaction ConditionsOperation in experiment
[1-(4-Amino-3-chlorophenyl)pyrrolidin-3-yl]dimethylamine Dimethylaminopyrrolidine was treated with 3-chloro-1-fluoro-4-nitrobenzene and subsequently reduced by method C-a. This resulted in the product with the molecular weight of 239.75 (C12H18ClN3); MS (ESI): 239 (M+H+), 240 (M+H+),
  • 39
  • [ 109-01-3 ]
  • [ 2106-50-5 ]
  • [ 1059705-52-0 ]
YieldReaction ConditionsOperation in experiment
88% With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 1h; Example 240 Synthesis of 1-(3-chloro-4-nitrophenyl)-4-methylpiperazine <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (1 g, 5.7 mmol) was dissolved in DMF (10 mL). 1-methylpiperazine (760 muL, 6.8 mmol) and then K2CO3 (1.57 g, 11.4 mmol) were added and the reaction was placed in a 100 C. oil bath. After 1 h, the solution was cooled to 23 C., then added to H2O (75 mL). The precipitate was filtered, washed with H2O (?25 mL), then dried overnight (50 C., 25 mmHg) to provide 1-3-chloro-4-nitrophenyl)-4-methylpiperazine (1.28 g, 88%) as a maize colored solid. The compounds described in the following table were prepared using chemistries similar to those exemplified in Example 240. All compounds were characterized by LCMS.
88% With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 1h; <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (1 g, 5.7 mmol) was dissolved in DMF (10 mL). 1-methylpiperazine (760 muL, 6.8 mmol) and then K 2CO 3 (1.57 g, 11.4 mmol) were added and the reaction was placed in a 100 C. oil bath. After 1 h, the solution was cooled to 23 C., then added to H 2O (75 mL). The precipitate was filtered, washed with H 2O (?25 mL), then dried overnight (50 C., 25 mmHg) to provide 1-3-chloro-4-nitrophenyl)-4-methylpiperazine (1.28 g, 88%) as a maize colored solid.
62% With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 3h; <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (1.0 eq, 1 g, 5.7 mmol), N-methyl piperazine (1.2 eq, 1.18 g, 6.84 mmol), potassium carbonate (2.0 eq, 1.6 g, 11.6 mmol) were stirred at 100 C. in DMF for 3 hours. The mixture was cooled down and diluted with water. The material was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and the solvent evaporated in vacuo. After trituration in diethylether and filtration, 1-(3-chloro-4-nitrophenyl)-4-methylpiperazine was isolated as a solid (0.9 g, 62%). LCMS (ES): m/z 256 [M+1]+.
With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 16h;Heating / reflux; A solution of <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (4.3 g), 1-methylpiperazine (2.99 mL) and DIPEA (5.55 mL) in THF (100 mL) was heated at reflux for 16h. The mixture was then concentrated in vacuo and the residue was purified by FCC eluting with DCM initially then using 2.5-10% MeOH in DCM. The title compound was thus obtained as a yellow solid; m/z: MH+ 256.

  • 40
  • [ 611-06-3 ]
  • [ 2106-50-5 ]
  • [ 446-35-5 ]
  • 41
  • [ 288-88-0 ]
  • [ 2106-50-5 ]
  • [ 856452-73-8 ]
YieldReaction ConditionsOperation in experiment
49A: 1-(2-Chloro-4-nitro-phenyl)-1H-[1,2,4]triazole 1.7 g of 1,2,4 triazole was dissolved in 70 ml of DMF and 1 g of NaH (60% in oil)was added. The mixture was stirred for 30 mn at RT and 1 equivalent <strong>[2106-50-5]2-chloro-4-fluoro-nitrobenzene</strong> was added. The reaction mixture was stirred at RT for 1 day and water was added. The reaction mixture was extracted with dichloromethane, the dichloromethane phase was washed three times with water and evaporated. The residue was triturated in isopropyl ether to give 1.5 g of a yellow powder used as such in the next step. 1H NMR (DMSO-d6): 9.15 (1H,s), 8.62 (1H,d), 8.46(1H,m), 8.35(1H, s), 7.95 (1H,d)
  • 42
  • [ 2106-50-5 ]
  • 4-(2-ethyl-5-hydroxyphenyl)-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione [ No CAS ]
  • [ 1235831-02-3 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 0.666667h;Microwave irradiation; Step 2: Preparation of 4-[5-(3-chloro-4-nitrophenoxy)-2-ethylphenyl]-2,2,6,6-tetramethylpyran-3,5- dione.; A mixture of 4-(2-ethyl-5-hydroxyphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (100 mg, 0.34 mmol), <strong>[2106-50-5]2-chloro-4-fluoro-1-nitrobenzene</strong> (72 mg, 0.41 mmol), and potassium carbonate (1 10 mg, 0.69 mmol) in Lambda/,Lambda/-dimethylformamide (2 ml) is heated to 140 0C under microwave irradiation for 40 minutes. The mixture is cooled to room temperature, poured into 2M aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract is washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-[5-(3-chloro-4-nitro-phenoxy)- 2-ethylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione.
  • 43
  • [ 40248-84-8 ]
  • [ 2106-50-5 ]
  • [ 100-39-0 ]
  • [ 1007165-67-4 ]
YieldReaction ConditionsOperation in experiment
37% (3-(Benzyloxy)phenyl)(3~chloro-4-nUrophenyl)sulfane (2a); <n="78"/>The product was purified by silica gel column chromatography using the Combi- Flash system (Hex:EtOAc) as yellowish oil in 37% (1.10 g). Proton NMR and LC analyses confirmed the desired product with purity greater than 95%. TLC (1 :4 EtOAc:Hex), Rf= 0.6; 1H NMR (400 MHz, CDCl3) delta 7.78 (d, IH5 J= 8.4 Hz)3 7.31-7.43 (m, 6H), 7.20 (d, IH, J= 2.0 Hz), 7.05-7.10 (m, 3H), 7.02 (dd, IH, J= 8.4 Hz, J= 1.6 Hz), 5.08 (s, 2H).
  • 44
  • [ 2106-50-5 ]
  • [ 760968-77-2 ]
  • [ 951667-42-8 ]
YieldReaction ConditionsOperation in experiment
36% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 1h; A mixture of methyl 5-hydroxy-2-[(4-methylphenyl)sulfonyl]aminobenzoate (354 mg mg, 1.07 mmol), <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (201 mg, 1.14 mmol), and potassium carbonate (370 mg, 2.67 mmol) in DMF (10 mL) was stirred at 80 C. for 1 hour. The reaction was diluted with H2O (50 mL) and extracted with EtOAc (2×50 mL). The EtOAc-extracts were washed once more with H2O (50 mL). The combined organic extracts were dried (Na2SO4), filtered, and evaporated to dryness in vacuo. The crude product was purified by column chromatography (EtOAc/heptane: 1/2) and then recrystallized from EtOAc/heptane to obtain the desired compound (182 mg, 36%, purity (LC) n.d.).NMR: 1H (300 Mhz, CDCl3): delta 10.45 (s, 1H), 7.92 (d, J=9.00 Hz, 1H), 7.77-7.70 (m, 3H), 7.59 (d, J=2.70 Hz, 1H), 7.26-7.15 (m, 4H), 6.93 (d, J=2.70 Hz, 1H), 6.83 (dd, J=2.70 Hz and J=9.00 Hz, 1H), 3.86 (s, 3H), 2.39 (s, 3H).MS: [M+H]+=447
  • 45
  • [ 199175-10-5 ]
  • [ 2106-50-5 ]
  • [ 1301190-06-6 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 0.916667h;Inert atmosphere; Microwave irradiation; Example 1805-[4-(l-[(3S)-l-(Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-6-fluoro-lH- benzimidazol-2-yl)phenyl] -lH-indazole(a) 1,1-Dimethylethyl (3S)-3-[(5-fluoro-2-nitrophenyl)amino]methyl}-l- pyrrolidinecarboxylate2-Chloro-4-fluoro-l -nitrobenzene (1.8 g, 10.25 mmol). 1,1-dimethylethyl (3S)-3- (aminomethyl)-l -pyrrolidmecarboxylate (2.7 g, 13.48 mmol) Cs2C03 (4.8 g, 14.73 mmol), Pd(OAc)2 (.126 g, 0.561 mmol) and BINAP (.59 g, 0.948 mmol) were suspended in toluene (16 mL) in a microwave vial under nitrogen. The reaction mixture was heated in a microwave reactor at 100 C for 45 min. An additional aliquot Pd Pd(OAc)2 (~ 100 mg) was added and the reaction heated an additional 10 min in the microwave reactor. The reaction mixture was filter and partitioned between EtOAc and aqueous NaHC03. The EtOAc layer was washed with brine, dry over sodium sulfate, filtered, and evaporated to dryness. The crude 1,1-dimethylethyl (3S)-3-[(5-fluoro-2-nitrophenyl)amino]methyl}-l- pyrrolidinecarboxylate was purified by silica gel column chromatography using a gradient of 0-10% IPA/EtOAc and used without further characterization.
  • 46
  • [ 2106-50-5 ]
  • [ 1331943-24-8 ]
  • [ 1423007-32-2 ]
YieldReaction ConditionsOperation in experiment
65% With potassium carbonate; In 1,2-dimethoxyethane; water; at 20 - 100℃;Sealed tube; Step 1 : 6-(N-(3-Chloro-4-nitrophenyl)methylsulfonamido)-2-(4-chlorophenyl)-5- cyclopropyl-N-methylbenzofuran-3-carboxamide A mixture of 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-(methylsulfonamido)benzofuran- 3-carboxamide (2.00 g, 4.77 mmol), 2-choro-4-fluoronitrobenzene (1 .68 g, 9.55 mmol), and potassium carbonate (1 .98 g, 14.3 mmol) in 4: 1 DME/water (20 mL) in a sealed vessel was heated to 100C with stirring. After 18 hours the mixture was treated with an additional 2.00 g portion of potassium carbonate, heated at 100C for another 15 hours, and then stirred at RT for 3 days. The mixture was partitioned between EtOAc and water. After separating the phases, the aqueous portion was extracted with two additional portions of EtOAc. The combined EtOAc solutions were washed with water (2x), brine (1x), dried over sodium sulfate and concentrated to dryness at reduced pressure. The crude material was subjected to flash chromatography (silica gel, gradient from DCM to 7:3 DCM/EtOAc) to afford a tacky, yellow foam. This material was crystallized from hexane/EtOAc to give the title compound (1.78 g, 65%) as a light yellow solid. LCMS {m/z, ES+) = 574 (M+H+).
65% With potassium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 33h; Step 1 : 6-(N-(3-Chloro-4-nitrophenyl)methylsulfonamido)-2-(4-chlorophenyl)-5-cyclopropyl-N- methylbenzofuran-3-carboxamide A mixture of 2-(4-chlorophenyl)-5-cyclopropyl-N-methyl-6-(methylsulfonamido)benzofuran-3- carboxamide (2.00 g, 4.77 mmol), 2-choro-4-fluoronitrobenzene (1.68 g, 9.55 mmol), and potassium carbonate (1 .98 g, 14.3 mmol) in 4:1 DME/water (20 ml.) in a sealed vessel was heated to 100C with stirring. After 18 hours the mixture was treated with an additional 2.00 g portion of potassium carbonate, heated at 100C for another 15 hours, and then stirred at RT for 3 days. The mixture was partitioned between EtOAc and water. After separating the phases, the aqueous portion was extracted with two additional portions of EtOAc. The combined EtOAc solutions were washed with water (2x), brine (1x), dried over sodium sulfate and concentrated to dryness at reduced pressure. The crude material was subjected to flash chromatography (silica gel, gradient from DCM to 7:3 DCM/EtOAc) to afford a tacky, yellow foam. This material was crystallized from hexane/EtOAc to give the title compound (1.78 g, 65%) as a light yellow solid. LCMS {m/z, ES+) = 574 (M+H+).
  • 47
  • [ 691856-35-6 ]
  • [ 2106-50-5 ]
  • [ 1423007-28-6 ]
YieldReaction ConditionsOperation in experiment
64% With potassium carbonate; In 1,2-dimethoxyethane; water; at 20 - 100℃; for 88h;Sealed tube; Step 1 : 6-(N-(3-Chloro-4-nitrophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)- N-methylbenzofuran-3-carboxamide A mixture of 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran- 3-carboxamide (12.5 g , 31.1 mmol), <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (10.9 g, 62.1 mmol) and potassium carbonate (12.9 g, 93.0 mmol) in 130 mL of 4:1 DME/water in a sealed flask was heated to 100C with stirring. An identical 12.5 g scale reaction was set up in a second sealed vessel. The reaction vessels were maintained at 100C for 70 hours, cooled to RT, and stirred for an additional 18 hours. The combined reaction mixtures were partitioned between EtOAc (300 mL) and water (600 mL), and the phases separated. The aqueous solution was extracted with two additional 150 mL portions of EtOAc. The combined EtOAc solutions were washed with half saturated brine (1 x), saturated brine (1x), dried over sodium sulfate and concentrated to dryness at reduced pressure. The resulting yellow-brown solid was recrystallized from EtOAc/ether to give the title compound (22.3 g, 64%) as an off-white solid. LCMS {m/z, ES+) = 558 (M+H+).
64% With potassium carbonate; In 1,2-dimethoxyethane; water; at 100℃; for 70h;Sealed tube; Step 1 : 6-(N-(3-Chloro-4-nitrophenyl)methylsulfonamido)-5-cyclopmethylbenzofuran-3-carboxamide A mixture of 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3- carboxamide (12.5 g , 31 .1 mmol), <strong>[2106-50-5]2-chloro-4-fluoronitrobenzene</strong> (10.9 g, 62.1 mmol) and potassium carbonate (12.9 g, 93.0 mmol) in 130 ml. of 4:1 DME/water in a sealed flask was heated to 100C with stirring. An identical 12.5 g scale reaction was set up in a second sealed vessel. The reaction vessels were maintained at 100C for 70 hours, cooled to RT, and stirred for an additional 18 hours. The combined reaction mixtures were partitioned between EtOAc (300 ml.) and water (600 ml_), and the phases separated. The aqueous solution was extracted with two additional 150 ml. portions of EtOAc. The combined EtOAc solutions were washed with half saturated brine (1 x), saturated brine (1 x), dried over sodium sulfate and concentrated to dryness at reduced pressure. The resulting yellow-brown solid was recrystallized from EtOAc/ether to give the title compound (22.3 g, 64%) as an off-white solid. LCMS {m/z, ES+) = 558 (M+H+).
  • 48
  • [ 2106-50-5 ]
  • 6-fluoro-1-(3-methoxyphenyl)-1H-benzo[d][1,2,3]triazole [ No CAS ]
  • 52
  • [ 143-16-8 ]
  • [ 2106-50-5 ]
  • [ 1542259-21-1 ]
YieldReaction ConditionsOperation in experiment
69% With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 72h; To a solution of <strong>[2106-50-5]2-chloro-4-fluoro-1-nitrobenzene</strong> (17.55 g, 0.10 mol) in DMF (100 mL) were added K2C03 (27.64 g, 0.20 mol) and dihexylamine (18.54 g, 0.10 mol) and the mixture was stirred at 90 C for 72 h. The mixture was cooled to rt and filtered. The filtrate was concentrated to 50 mL. The resulting solution was poured into 150 mL of DCM and washed with water (150 mL x 3), brine (150 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE / EtOAc (V / V)10: 1) to give the title compound as yellow oil (23.64 g, 69%).
69% With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 72h; To a solution of <strong>[2106-50-5]2-chloro-4-fluoro-1-nitrobenzene</strong> (17.55 g, 0.10 mol) in DMF (100 mL) were added K2CO3 (27.64 g, 0.20 mol) and dihexylamine (18.54 g, 0.10 mol) and the mixture was stirred at 90 C. for 72 h. The mixture was cooled to rt and filtered. The filtrate was concentrated to 50 mL. The resulting solution was poured into 150 mL of DCM and washed with water (150 mL*3), brine (150 mL), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=10:1) to give the title compound as yellow oil (23.64 g, 69%).
  • 53
  • [ 2106-50-5 ]
  • [ 1542259-22-2 ]
  • 54
  • [ 2106-50-5 ]
  • [ 1542259-23-3 ]
 

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