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Chemical Structure| 156150-67-3 Chemical Structure| 156150-67-3

Structure of 156150-67-3

Chemical Structure| 156150-67-3

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Product Details of [ 156150-67-3 ]

CAS No. :156150-67-3
Formula : C6H3ClFI
M.W : 256.44
SMILES Code : IC1=CC=C(F)C(Cl)=C1
MDL No. :MFCD00042210
InChI Key :OMASDGWBVAVFQZ-UHFFFAOYSA-N
Pubchem ID :2724605

Safety of [ 156150-67-3 ]

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

Computational Chemistry of [ 156150-67-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 44.13
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.24
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

3.3
Log Po/w (WLOGP)?

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

3.5
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.

4.22
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

3.89
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.43

Water Solubility

Log S (ESOL):?

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

-4.0
Solubility 0.0255 mg/ml ; 0.0000995 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.

-2.98
Solubility 0.271 mg/ml ; 0.00106 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

-4.25
Solubility 0.0146 mg/ml ; 0.0000568 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

Low
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.

-5.52 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

1.0
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<0.0
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)

2.27

Application In Synthesis of [ 156150-67-3 ]

* 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 [ 156150-67-3 ]

[ 156150-67-3 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 156150-67-3 ]
  • [ 462-06-6 ]
  • [ 348-51-6 ]
  • [ 71-43-2 ]
  • 4
  • [ 675-10-5 ]
  • [ 463-49-0 ]
  • [ 156150-67-3 ]
  • 3-[2-(3-chloro-4-fluorophenyl)prop-2-en-1-yl]-4-hydroxy-6-methyl-2H-pyran-2-one [ No CAS ]
  • 5
  • [ 1076-38-6 ]
  • [ 463-49-0 ]
  • [ 156150-67-3 ]
  • 3-{2-[3-chloro-4-fluorophenyl]prop-2-en-1-yl}-4-hydroxy-2H-chromen-2-one [ No CAS ]
  • 6
  • [ 13252-83-0 ]
  • [ 463-49-0 ]
  • [ 156150-67-3 ]
  • 3-[2-(3-chloro-4-fluorophenyl)prop-2-en-1-yl]-4-hydroxy-6-methyl-2H-chromen-2-one [ No CAS ]
  • 7
  • [ 156150-67-3 ]
  • [ 1122-91-4 ]
  • 3'-chloro-4'-fluoro[1,1'-biphenyl]-4-carbaldehyde [ No CAS ]
  • 8
  • [ 959918-13-9 ]
  • [ 156150-67-3 ]
  • [ 1008524-33-1 ]
YieldReaction ConditionsOperation in experiment
25% With caesium carbonate; In N,N-dimethyl-formamide; at 65℃; for 18h; EXAMPLE 42-(2-Chloro-4-iodorhohenylaminoV5.5-dimethyl-8-oxo-5,6J.8-tetrahvdro-4H-thienor2,3- clazepine-S-carboxylic acid ethyl ester; Caesium carbonate (2.77 g, 8.51 mmol) and 2-chloro-4-iodo-l-fluorobenzene (2.18 g, 8.51 mmol) were added to a solution of Intermediate 6 (2.0 g, 7.09 mmol) in DMF (20 mL) and heated at 650C for 18 h. Brine (100 mL) was added to the reaction and the mixture extracted with DCM (3 x 50 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The residual DMF was azeotroped with heptane. The crude product was purified by chromatography (silica, 0-30% EtOAc in DCM) to give the title compound as a cream solid (916 mg, 25%). deltaeta (DMSO-d6) 10.60 (IH, s), 8.01 (IH, t, J 5.0 Hz), 7.95 (IH, d, J2.0 Hz), 7.78 (IH, dd, J 8.6, 2.0 Hz), 7.54 (IH, d, J 8.6 Hz), 4.32 (2H, q, J 7.1 Hz), 2.91 (2H, s), 2.85 (2H, d, J 5.2 Hz), 1.33 (3H, t, J 7.1 Hz), 0.99 (6H, s). LCMS (ES+) RT 3.81 minutes, 519 (M+H)+.
25% With caesium carbonate; In N,N-dimethyl-formamide; at 65℃; for 18h; INTERMEDIATE 4; 2-(2-ChloiO-4-iodophenylamino)-5,5-dimethyl-8-oxo-5,6.7.8-tetrahydro-4H-thieno["2,3- c"|azepine-3-carboxylic acid ethyl ester Caesium carbonate (2.77 g, 8.51 mmol) and 2-chloro-4-iodo-l-fluorobenzene(2.18 g, 8.51 mmol) were added to a solution of 2-amino-5,5-dimethyl-8-oxo-5, 6,7,8- tetrahydro-4i7-thieno[2,3-c]azepine-3-carboxylic acid ethyl ester (WO 2007/141504, Intermediate 20) (2.0 g, 7.09 mmol) in DMF (20 mL) and heated at 650C for 18 h. Brine (100 mL) was added to the reaction and the mixture extracted with DCM (3 x 50 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The residual DMF was azeotroped with heptane. The crude product was purified by chromatography (silica, 0-30% EtOAc in DCM) to give the title compound as a cream solid (916 mg, 25%). deltaH (DMSO-d6) 10.60 (IH, s), 8.01 (IH, t, J 5.0 Hz), 7.95 (IH, d, J <n="32"/>2.0 Hz), 7.78 (IH, dd, J8.6, 2.0 Hz), 7.54 (IH, d, J8.6 Hz), 4.32 (2H, q, J7.1 Hz), 2.91 (2H, s), 2.85 (2H, d, J5.2 Hz), 1.33 (3H, t, J7.1 Hz), 0.99 (6H, s). LCMS (ES+) RT 3.81 minutes, 519 (M+H)+.
  • 9
  • [ 463-49-0 ]
  • [ 156150-67-3 ]
  • [ 89-25-8 ]
  • 4,4-bis[(3-chloro-4-fluorophenyl)prop-2-en-1-yl]-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one [ No CAS ]
  • 10
  • [ 769-42-6 ]
  • [ 463-49-0 ]
  • [ 156150-67-3 ]
  • 5,5-bis[2-(3-chloro-4-fluorophenyl)prop-2-en-1-yl]-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione [ No CAS ]
  • 11
  • [ 463-49-0 ]
  • [ 156150-67-3 ]
  • [ 1076-59-1 ]
  • 4,4-bis[2-(3-chloro-4-fluorophenyl)prop-2-en-1-yl]-3-phenylisoxazol-5(4H)-one [ No CAS ]
  • 14
  • [ 98830-89-8 ]
  • [ 156150-67-3 ]
  • [ 306297-99-4 ]
YieldReaction ConditionsOperation in experiment
78% With copper(l) iodide;tetrakis(triphenylphosphine) palladium(0); In DMF (N,N-dimethyl-formamide); at 20℃; for 21h; To the stannane (0.39 g, 0.95 mmol) in DMF (10 ml) was added the 2-chloro-4-fluoroiodobenzene (0.73 g, 2.86 mmol), Cul (0.19 g, 1.05 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.11 g, 0.095 mmol). The reaction was stirred at RT under N2 for 21 h. The reaction mixture was added to Et2O and the heterogeneous solution filtered through a bed of celite, washing with EtOAc. The filtrate was washed with water and brine and dried (MgSO4). Filtration and evaporation of the solvent in vacuo afforded a residue that was preadsorbed on silica gel. Purification by silica gel chromatography (4% EtOAc/hexane) yielded the arylacrylate (0.19 g, 78%), which was used directly in the next step.
  • 15
  • [ 329202-22-4 ]
  • [ 156150-67-3 ]
  • [ 866686-85-3 ]
YieldReaction ConditionsOperation in experiment
70% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 60℃; for 5h; Add bis (triphenylphosphine) palladium (II) dichloride (64 mg, 0. 091 mmol), copper (I) iodide (35 mg, 0. 18 mmol), and 3-chloro-5-ethynylpyridine, (prepared as described in PREPARATION 27), (250 mg, 1. 8 mmol) to a solution of 2-chloro-1-fluoro- 4-iodobenzene (560 mg, 2. 2 mmol) in triethylamine (3. 8 mL, 27 mmol) and heat at 60 C for 5 h. Cool to room temperature and concentrate. Purify by silica gel chromatography, eluting with 50 : 50 to 100 : 0 dichloromethane : hexanes, followed by a second silica gel chromatography, eluting with 100 : 0 to 90 : 10 hexanes : ethyl acetate, to give the title compound as a white solid (340 mg, 70%). 1H NMR (300 MHz, CDCl3) 8 7. 11-7. 19 (t, J = 8. 6 Hz, 1H), 7. 38-7. 46 (m, 1H), 7. 58- 7. 64 (m, 1H), 7. 77-7. 81 (t, J = 2. 0 Hz, 1H), 8. 52-8. 55 (d, J = 2. 3 Hz, 1H), 8. 60-8. 63 (d, J = 1. 7 Hz, 1H) ; MS (APCI) : m/z = 266 [M+H] +.
  • 16
  • [ 686768-50-3 ]
  • [ 156150-67-3 ]
  • [ 866685-80-5 ]
YieldReaction ConditionsOperation in experiment
93% With triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; at 60℃; for 5h; Add bis (triphenylphosphine) palladium (II) dichloride (110 mg, 0. 15 mmol), copper (I) iodide (57 mg, 0. 30 mmol), and 3-ethynyl-5-methoxypyridine, (prepared as described in PREPARATION 10), (400 mg, 3. 0 mmol) to a solution of 2-chloro-1-fluoro- 4-iodobenzene (0. 46 mL, 3. 6 mmol) in triethylamine (6. 3 mL, 45. 0 mmol-) and heat at 60 C for 5 h. Cool to room temperature and concentrate. Purify the residue by silica gel chromatography, eluting with a gradient of 100 : 0 to 80 : 20 dichloromethane : ethyl acetate, followed by a second silica gel chromatography, eluting with 67 : 33 to 60 : 40 hexanes : ethyl acetate, to give the title compound as a white solid (730 mg, 93%). 1H NMR (300 MHz, Cd13) 8 3. 88 (s, 3H), 7. 11-7. 18 (t, J = 8. 7 Hz, 1H), 7. 28-7. 32 (m, 1H), 7. 39-7. 46 (m, 1H), 7. 57-7. 63 (m, 1H), 8. 27-8. 30 (d, J = 2. 8 Hz, 1H), 8. 34-8. 37 (d, J = 1. 5 Hz, 1H) ; MS (APCI) : m/z = 262 [M+H]+.
  • 17
  • [ 866683-29-6 ]
  • [ 156150-67-3 ]
  • [ 866685-08-7 ]
YieldReaction ConditionsOperation in experiment
31% With tetrabutyl ammonium fluoride; triethylamine;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; at -78 - 70℃; Stir 5-trimethylsilanylethynyl-nicotinonitrile (300 mg, 1. 5 mmol), (prepared essentially as described in PREPARATION 3), <strong>[156150-67-3]2-chloro-1-fluoro-4-iodobenzene</strong> (390 mg, 1. 5 mmol), bis (triphenylphosphine) palladium (II) dichloride (50 mg, 0. 08 mmol) and copper (I) iodide (20 mg, 0. 15 mmol) in triethylamine (15 mL) under nitrogen and cool to - 78C. Add a 1 M solution of tetrabutylammonium fluoride (1. 5 mL) in tetrahydrofuran and warm to room temperature and then heat at 70 C until complete by thin layer chromatography. Concentrate and purify the residue by silica gel chromatography, eluting with hexanes : ethyl acetate, and then recrystallize from hexanes : ethyl acetate to give the title compound (120 mg, 31%). 1H NMR (400 MHz, CDCl3) 6 7. 18 (t, J = 8. 8 Hz, 1H), 7. 46-7. 42 (m, 1H), 7. 62 (dd, J = 6. 8 Hz, 2. 0 Hz, 1H), 8. 06 (t, J = 2. 2 Hz, 1H), 8. 82 (d, J = 1. 8 Hz, 1H), 8. 91 (d, J = 2. 2 Hz, 1H) ; HRMS calcd for C14H7ClFN2 257. 0282. Found 257. 0266 ; Anal. Calcd for C14H6ClFN2 : C, 65. 52 ; H, 2. 37 ; N, 10. 91. Found : C, 65. 59 ; H, 2. 48 ; N, 10. 67.
  • 18
  • [ 156150-67-3 ]
  • [ 147081-44-5 ]
  • [ 915001-95-5 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; ethylene glycol;copper(l) iodide; for 46h;Heating / reflux; To a 50 ml of isopropyl alcohol solution containing 15.0 g of 3 (S) -aminopyrrolidine-1-carboxylic acid tert-butyl ester (80.5 mmol) and 24.8 g of 2-chloro-l-fluoro-4-iodobenzene(96.7 mmol) were added 1.54 g of copper (I) iodide (8.1 mmol),9.0 ml of ethylene glycol (10.1 mmol) and 34.2 g of potassium phosphate (161 mmol) , and heated under reflux under a nitrogen atmosphere for 46 hours. The reaction solution was cooled to room temperature and filtered using Celite. The substance remained in the filter was washed with ethyl acetate and the filtrate was concentrated under reduced pressure together with the washings, and the residue was purified by silica gel column chromatography (n-hexane : ethyl acetate = 4 : 1) . The solvent was distilled off under reduced pressure, and the residue was recrystallized from diethyl ether to thereby obtain 15.9 g of white powdery 3 (S)- (3- chloro-4-fluorophenylamino)pyrrolidine-l-carboxylic acid tert- butyl ester. 1H-NMR(CDCl3) deltappm: 1.47(9H,s), 1.78-1.96 (lH,m) , 2.10-2.28 (IH,m) , 2.10-2.28 (lH,m) , EPO <DP n="69"/>3.11-3.30 (IH,m), 3.30-3.56 (2H,m) , 3.57-3.79 (2H,m) , 3.85- 4.03(lH,m), 6.38-6.47 (IH,m) , 6.60 (IH, dd, J=6. OHz, J=2.9Hz) , 6.90- 7.00 (IH,m) .
  • 19
  • [ 1043903-16-7 ]
  • [ 156150-67-3 ]
  • [ 1043902-15-3 ]
YieldReaction ConditionsOperation in experiment
12.8% With cesium acetate;palladium diacetate; tris(para-trifluoromethyl)phenyl phosphine; In N,N-dimethyl-formamide; at 125℃; for 18.5h;Product distribution / selectivity; Example 22 : 5-([l ,2,4] triazolo [1 ,5-a] pyridin-6-yl)-4-(3-chloro-4-fluorophenyl)-2,2- dimethylfuran-3(2H)-one; [00195] Cesium acetate (167 mg, 0.000872 mol) was added to a round bottom flask and dried under vacuum at 125 C for 2 hours. Palladium acetate (0.98 mg, 0.0000044 mol), tris(4-trifluoromethylphenyl)phosphine (8.1 mg, 0.000017 mol), and N,N- dimethylformamide (1.7 mL, 0.022 mol) were added to the dried cesium acetate and the mixture stirred for 30 min. 5-([l,2,4]triazolo[l,5-a]pyridin-6-yl)-2,2-dimethylfuran-3(2H)- one (100.0 mg, 0.0004362 mol) and 2-chloro-l-fluoro-4-iodobenzene (112 mg, 0.000436 mol) in N,N-dimethylformamide (1.7 mL, 0.022 mol) were added and the mixture stirred at 125 0C <n="60"/>for 18 hr. The mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered, and concentrated to give a yellow oil. The yellow oil was purified on HPLC eluting with acetonitrile: water (0.1% TFA) to give 20.0 mg (12.8%) of the title compound as a yellow solid.1H NMR (300 MHz, Methanol-^) delta 9.19 (s, IH), 8.49 (s, IH), 7.75 (m, 3H), 7.29 (m, 2H), 1.59 (s, 6H). MS (ESP+) m/z 358.09.
  • 20
  • [ 156150-67-3 ]
  • [ 31383-81-0 ]
  • [ 1056452-45-9 ]
  • [ 1056452-44-8 ]
YieldReaction ConditionsOperation in experiment
27% A mixture of compound IV (0.314 g, 1 mmol), copper(l)tris(triphenyl- phosphine)bromide (372 mg, 0.4 mmol), Cs2CO3 (977 mg, 3 mmol), and toluene (15 mL) was heated under argon at 110 0C for 5 min. The aryl iodide (2 mmol) was added via syringe and the mixture was stirred at 110 0C for 1-2 days. After cooling, the mixture was filtered through a small pad of silica gel, concentrated and purified by chromatography, furnishing the di-arylated compound as the minor product and the mono-arylated as the major product. The subsequent hydrolysis was carried out in accordance with the procedure described in Method A.
  • 21
  • [ 4341-76-8 ]
  • [ 156150-67-3 ]
  • [ 1187324-91-9 ]
YieldReaction ConditionsOperation in experiment
6.5% With sodium azide;copper(ll) sulfate pentahydrate; sodium carbonate; sodium L-ascorbate; L-proline; In water; dimethyl sulfoxide; at 20 - 65℃; Intermediate 5: Ethyl 1-(3-chloro-4-fluorophenyl)-5-methyl-1 H-1 ,2,3-triazole-4- carboxylate; To a mixture of <strong>[156150-67-3]2-chloro-1-fluoro-4-iodobenzene</strong> (0.5 g, 1.950 mmol) and ethyl 2- butynoate (0.227 ml, 1.950 mmol) in water/DMSO (0.22ml/2ml) at room temperature was added L-proline (0.045 g, 0.390 mmol), sodium carbonate (0.041 g, 0.390 mmol), sodium azide (0.152 g, 2.340 mmol), sodium l-ascorbate (0.039 g, 0.195 mmol) and copper(ll) sulfate pentahydrate (0.024 g, 0.097 mmol) (in this order) and the mixture was heated at 65 0C overnight. On cooling to room temperature, the mixture was quenched with aqueous ammonia (1 ml) and EtOAc (20ml) and water (20 ml) were added. The two phases were separated, and the aqueous phase was extracted with EtOAc (3 x 30 ml). All organic phases were combined and washed with water/brine (50ml) repeatedly. The organic phase was dried over sodium sulfate, filtered and the solvent was evaporated to afford a crude product that was purified by MDAP to afford the title compound (6.5%); MH+=284.
  • 22
  • [ 1777-03-3 ]
  • [ 156150-67-3 ]
  • [ 1150542-40-7 ]
  • 23
  • [ 156150-67-3 ]
  • [ 107-18-6 ]
  • [ 1057671-07-4 ]
  • 24
  • [ 156150-67-3 ]
  • [ 2114-00-3 ]
  • [ 1206768-11-7 ]
  • 25
  • [ 156150-67-3 ]
  • [ 93267-04-0 ]
  • [ 915040-50-5 ]
  • [ 1310358-53-2 ]
  • 26
  • [13C15N]copper(I) cyanide [ No CAS ]
  • [ 156150-67-3 ]
  • [ 1330003-86-5 ]
  • 27
  • [ 156150-67-3 ]
  • [ 1330003-87-6 ]
  • 28
  • [ 156150-67-3 ]
  • [ 1330003-88-7 ]
  • 29
  • [ 696-62-8 ]
  • [ 156150-67-3 ]
  • 3-chloro-4-fluoro-4'-methoxy-1,1'-biphenyl [ No CAS ]
  • 30
  • [ 500-99-2 ]
  • [ 156150-67-3 ]
  • 2-chloro-1-(3,5-dimethoxyphenoxy)-4-iodobenzene [ No CAS ]
  • 31
  • [ 156150-67-3 ]
  • [ 272-52-6 ]
  • [ 1383735-02-1 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;copper(l) iodide; cis-N,N'-dimethyl-1,2-diaminocyclohexane; In N,N-dimethyl-formamide; at 130℃; for 1h;microwave irradiation; A solution of L-1 (1.0 g, 8.4 mmol), Cul (960 mg, 5.4 mmol), K2CO3 (2.78 g, 20.2 mmol), N,N'-dimethyl-l,2-diaminocyclohexane (0.130 mL, 0.84 mmol), and L-2 (2.8 g, 11 mmol) in 13 mL of DMF is warmed at 130C in a microwave reactor. After 1 hour, the reaction is diluted with saturated aqueous NH4C1 (50 mL) and NaHCO3 is added and the mixture is stirred for 30 minutes. EtOAc (200 mL) is added and the mixture is stirred overnight at room temperature. The mixture is extracted with EtOAc (3 x 50 mL). The combined organic layers are washed with saturated aqueous NH4CI (3 x 40 mL), dried over magnesium sulfate, filtered and concentrated. The residue is dissolved in 15 mL methanol and stirred at 80C for 30 minutes and allowed to cool for 1 hour. The material is collected by filtration, washed with hexanes, and dried to provide L-3.
  • 32
  • [ 156150-67-3 ]
  • [ 272-52-6 ]
  • [ 1383735-57-6 ]
  • 33
  • [ 768-94-5 ]
  • [ 1415409-74-3 ]
  • [ 156150-67-3 ]
  • [ 1415409-81-2 ]
  • 34
  • [ 170655-55-7 ]
  • [ 156150-67-3 ]
  • [ 1413285-76-3 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 70℃; for 13h; A round bottom flask is charged with 2-sulfanyl-N-(2,2,2-trifluoroethyl)acetamide (example 14, Step 3, 7.69 g), cesium carbonate (19.7 g), dimethylformamide (100 ml) then the suspension is stirred for 30 min at rt. A solution of <strong>[156150-67-3]3-chloro-4-fluoroiodobenzene</strong> (7.69 g) in dimethylformamide (50 ml) was added and the mixture is stirred at room temperature for 12 hours then 1 hour at 70C. The mixture was diluted with ethyl acetate (100 ml) then washed with water (5*100 ml), 2N hydrochloric acid solution, brine, then dried over sodium sulphate. The solvent was removed under reduced pressure to dryness to afford the crude as yellow solid (13 g). The residue was purified by flash column chromatography of the residue (ethyl acetate / heptanes) afforded the title product as a yellow solid (900 mg). lU NMR (400Mz, CDC13): delta 3.70 (s, 2H), 4.40 (m, 2H), 6.90 (d, 2H), 6.95 (br s, 1H), 7.48 (d, 2H), 7.76 (d, 2H). LCMS (Method E) RT 1.03 min, [M+H]+ 408/410.
  • 35
  • [ 1273324-41-6 ]
  • [ 156150-67-3 ]
  • C30H21ClFNO3 [ No CAS ]
 

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