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Chemical Structure| 612832-83-4 Chemical Structure| 612832-83-4

Structure of 612832-83-4

Chemical Structure| 612832-83-4

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Product Details of [ 612832-83-4 ]

CAS No. :612832-83-4
Formula : C13H12BClO3
M.W : 262.50
SMILES Code : ClC1=CC=C(OCC2=CC=CC=C2)C(B(O)O)=C1
MDL No. :MFCD04039000
InChI Key :SLERXVFZNNSBIX-UHFFFAOYSA-N
Pubchem ID :4198740

Safety of [ 612832-83-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 612832-83-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 12
Fraction Csp3 0.08
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 72.26
TPSA ?

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

49.69 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

2.92
Log Po/w (WLOGP)?

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

1.45
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.

2.07
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.57

Water Solubility

Log S (ESOL):?

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

-3.54
Solubility 0.0763 mg/ml ; 0.000291 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.

-3.62
Solubility 0.0623 mg/ml ; 0.000237 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

-4.57
Solubility 0.00708 mg/ml ; 0.000027 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

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

Yes
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.

-5.83 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

0.0
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

1.0 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)

2.25

Application In Synthesis of [ 612832-83-4 ]

* 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 [ 612832-83-4 ]

[ 612832-83-4 ] Synthesis Path-Downstream   1~35

  • 1
  • 3-(2-bromo-thiophen-3-yl)-benzenesulfonamide [ No CAS ]
  • [ 612832-83-4 ]
  • 3-[2-(2-benzyloxy-5-chloro-phenyl)-thiophen-3-yl]-benzenesulfonamide [ No CAS ]
  • 2
  • [ 612832-83-4 ]
  • [ 848188-14-7 ]
  • [ 848188-16-9 ]
  • 4
  • [ 887495-79-6 ]
  • [ 612832-83-4 ]
  • [ 887495-80-9 ]
  • 8
  • [ 100398-25-2 ]
  • [ 612832-83-4 ]
YieldReaction ConditionsOperation in experiment
74% Compound))) : (2-Benzyloxy-5-chlorophenyl)-boronic acid (WO 01/19814 A2) 2-Benzyloxy-5-chlorophenyl iodide (5g 0.0145 mol) in diethyl ether/tetrahydrofuran (100: 30) was cooled to-100C. n-Butyl lithium, 1.6M solution in hexanes (10mL, 0.016 mol) was added dropwise over 15min under nitrogen. The reaction mixture was then allowed to rise to-70C for 1 h. Triethylborate (9mL, 0.03 mol) was added dropwise under nitrogen. The cooling bath was then removed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then quenched with 2N hydrochloric acid (40mL) and stirred vigorously at room temperature for 1 h. The product was then extracted with ethyl acetate, dried over magnesium sulphate and evaporated down to an oil. Purification was carried out on a Biotage (90g cartridge) with ether/iso-hexane (50: 50) to give the required product (wt; 2.8g i. e. 74% yield).
74% 2- (Benzvloxv)-5-chloro-nhenvlboronic acid 2-(Benzyloxy)-5-chloro-iodobenzene (5g 0.0145 mol) in diethyl ether/tetrahydrofuran (100: 30) was cooled to-100C. n-Butyl lithium, 1.6M solution in hexanes (10mL, 0.016 mol) was added dropwise over 15min under nitrogen. The reaction mixture was then allowed to rise to-70C for 1 h. Triethylborate (9mL, 0.03 mol) was added dropwise under nitrogen. The cooling bath was then removed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then quenched with 2N hydrochloric acid (40mL) and stirred vigorously at room temperature for 1 h. The product was then extracted with ethyl acetate, dried over magnesium sulphate and evaporated down to an oil. Purification was carried out on silica gel with diethyl ether/iso-hexane (50: 50) to give the title compound (2.8g, 74% yield).
53% Butyllithium (11. 5 ml, 28.7 mmol, 2.5 M) was added, under nitrogen, over 10 minutes, to a solution of 2-BENZYLOXY-5-CHLORO-IODOBENZENE (9 g, 26.2 MMOL) in THF (40 ML) AT-100C. The reaction mixture was then warmed up AT-78C and stirred for 1 hour (AT-78C) before triisopropyl borate (18 ml, 78.4 MMOL) was added over 10 minutes. The reaction mixture was then warmed to room temperature before a solution of HCI (60 ml, 1 M) was added. The mixture was vigorously stirred for 1 1/2 hours. The organic phase was separated, washed sequentially with water and brine, dried (MGSO4) filtered and concentrated. The residue was triturated with a 30% solution of ether in iso-hexane and filtered to give the title compound (3.62g, 53%) as a white solid. 1H NMR (CDCI3) delta 5.12 (2H, s), 5.74 (2H, s), 6.91 (1H, d), 7.26 (1 H, s), 7,35-7. 41 (5H, m), 7.81 (1 H, s).
2-Benzvloxv-5-chlorophenvlboronic acid; A solution of 2M isopropylmagnesium chloride in diethyl ether (46. 5ml, 93 mmol) was added over 20 minutes to a solution of 2-benzyloxy-5-chloroiodobenzene (16.02g, 46.5 mmol) in dry THF (150m1) at-40C under nitrogen. After stirring for 1 hour at-40 C the mixture was cooled to-78 C and trimethyl borate (9.67g, 93 mmol) was added over 5 minutes. The resulting mixture was allowed to warm to room temperature and 2M hydrochloric acid (200mi) was added and stirred vigorously for 15 minutes. The organic phase was separated, dried (magnesium sulphate), evaporated to dryness and triturated with iso-hexane to give 11.9g of off-white solid. LC/MS: Rt 3.4, [2MH-] 637.3.

  • 9
  • [ 612832-83-4 ]
  • 3-[2-(2-benzyloxy-5-chloro-phenyl)-pyridin-3-yl]-benzoic acid [ No CAS ]
  • 11
  • [ 100-39-0 ]
  • (1R,2R)-O-Merrifield bound N-(2-hydroxy-1-methyl-2-phenyl-ethyl)-N-methyl-2'-phenylacetamide [ No CAS ]
  • [ 612832-83-4 ]
  • 12
  • [ 151038-76-5 ]
  • [ 612832-83-4 ]
YieldReaction ConditionsOperation in experiment
A solution of butyl lithium (1.6 M in hexane) (50 ml) was added drop wise to a stirredsolution of the product from step a) (23 g) in diethylether (300 ml) at -70 C. After 1 h afurther 18 ml of butyl lithium was added, left for 0.75 h, then trimethylborate (10 ml) addedand the mixture warmed to RT and left for 16 h. 2 M Hydrochloric acid (100 ml) was added,stirred for Ih then the organic layer separated and extracted with aqueous sodium hydroxidesolution. The basic layer was acidified with 2 M hydrochloric acid solution, extracted withdiethylether which was dried and evaporated under reduced pressure. The residue wastriturated with iso-hexane and filtered to give the sub-title compound (10.8 g)JH NMR CDC13: 8 7.82 (IH, d); 7.44-7.34 (6H, m) ; 6.90 (IH, d) ; 5.99 (2H, s) ; 5.12 (2H, s)
A solution of butyl lithium (1.6M in hexane) (50ML) was added dropwise to a stirred solution of the product from step (i) (23g) in diethylether (300ml) AT-70C. After lh a further 18ML of butyl lithium was added, left for 0.75h, then trimethylborate (10ML) added and the mixture warmed to RT and left for 16h. 2M Hydrochloric acid (100ml) was added, stirred for lh then the organic layer separated and extracted with aqueous sodium hydroxide solution. The basic layer was acidified with 2M hydrochloric acid solution, extracted with diethylether which was dried and evaporated under reduced pressure. The residue was triturated with iso-hexane and filtered. Yield 10.8g 1H NMR CDC13 : 5 7. 82 (1H, d); 7.44-7. 34 (6H, m); 6.90 (1H, d); 5.99 (2H, s); 5.12 (2H, S)
  • 13
  • [ 612832-83-4 ]
  • {6-[2-(2-benzyloxy-5-chloro-phenyl)-thiophen-3-yl]-pyridin-2-yl}-methanol [ No CAS ]
  • 14
  • [ 612832-83-4 ]
  • 6-[2-(2-benzyloxy-5-chloro-phenyl)-thiophen-3-yl]-pyridine-2-carboxylic acid [ No CAS ]
  • 15
  • [ 690260-68-5 ]
  • [ 612832-83-4 ]
  • [ 690259-69-9 ]
YieldReaction ConditionsOperation in experiment
51% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; for 16h;Heating / reflux; A mixture OF 5-(2'-BROMO-BIPHENYL-3-YL)-1H-TETRAZOLE (163MG, 0. 54MMOL), 2-BENZYLOXY-5- chlorobenzeneboronic acid (156mg, 0. 59mmol), potassium carbonate (589MG, 4. 33mmol), AND TETRAKIS (TRIPHENYLPHOSPHINE) PALLADIUM (0) (63MG, 0. 05MMOL) IN1 : 1 TOLUENE/ETHANOL (5ML) was stirred and heated under nitrogen for 16 hours. After cooling the mixture was diluted with dichloromethane and water. The organic phase was dried and evaporated. The residue was chromatographed ELUTING with DICHLOROMETHANE/METHANOL (95: 5) to give the title compound as a colourless solid, (120mg 51%). 1H NMR (CDCl3) delta: 4.75 (2H, br s), 6.63 (1H, d, J=8Hz), 6.95-7. 50 (14H, m), 7.88 (1H, m), 7.96 (1 H, d, J=8Hz). LC/MS t=4.22 [MH+] 439.0, 441.0 (1 Cl).
  • 16
  • [ 690260-38-9 ]
  • [ 612832-83-4 ]
  • [ 690260-39-0 ]
YieldReaction ConditionsOperation in experiment
46% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 90℃; for 4.5h;Heating / reflux; 2'-Bromo-biphenyl-3-carboxylic acid ethyl ester (157mg, 0. 5MMOL), 2-benzyloxy-5-chloro- phenylboronic acid (157mg, 0. 6MMOL), tetrakis (TRIPHENYLPHOSPHINE) PALLADIUM (0) (66mg, 0. 06MMOL) and potassium carbonate (568mg, 4. 1 MMOL) was heated in toluene-ethanol (1: 1, 5ML) at 90C for 4.5 hours. Upon cooling, the mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried (NA2SO4), filtered and concentrated. The residue was purified by chromatography using Biotage with iso-hexane containing a gradient of ethyl acetate (1-5%) to yield the title compound (105MG, 46%) as a white solid. 1H NMR (CDCI3) delta (3H, t, J=7Hz), 4.28 (2H, q, J=7Hz), 4. 50-4. 80 (2H, br. s), 6.60 (1H, d, J=9Hz), 6.94-6. 98 (2H, m), 7.10 (1H, dd, J=3Hz, J=9Hz), 7.18-7. 25 (6H, m's excess), 7.35-7. 50 (4H, m), 7.83 (1 H, s), 7.88 (1 H, dt, J=1 HZ, J=7.5Hz). Rf 0.15 (5% EtOAc in iso-hexane). LC/MS t = 4.23 (100%), [MH+] 443.
  • 17
  • (2'-bromo-biphenyl-3-yl)-acetic acid methyl ester [ No CAS ]
  • [ 612832-83-4 ]
  • (2-benzyloxy-5-chloro[1,1';2',1"]terphenyl-3"-yl) acetic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 90℃; for 2h;Heating / reflux; A mixture of (2'-BROMO-BIPHENYL-3-YL)-ACETIC acid methyl ester (76 mg, 0.25 MMOL), 2- BENZYLOXY-5-CHLORO-PHENYL-BORONIC acid (72 mg, 0.275 MMOL), potassium carbonate (276 mg, 2 MMOL) and tetrakis (TRIPHENYLPHOSPHINE) PALLADIUM (0) (29 mg, 0.025 MMOL) in 1: 1 toluene/ethanol (3 ml) was heated and stirred at 90C under nitrogen for 2 hours. After cooling the mixture was diluted with water and diethyl ether and the organic phase dried (MGS04) and evaporated to dryness. The residue was purified by chromatography using Biotage with ethyl acetate/iso-hexane (1: 19) to yield the title compound as a colourless gum (112 mg, 98%). 1H NMR (CDCI3) 8 : 1.2 (3H, t, J=7Hz), 3.40 (2H, s), 4.06 (2H, q, J=7Hz), 4.66 (2H, br s), 6.59 (1H, d, J=8Hz), 6.96-7. 42 (15H, m).
  • 18
  • [ 690260-48-1 ]
  • [ 612832-83-4 ]
  • [ 690260-49-2 ]
YieldReaction ConditionsOperation in experiment
89% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 90℃; for 2h;Heating / reflux; A mixture of <strong>[612832-83-4]2-benzyloxy-5-chloro-phenyl-boronic acid</strong> (197 mg, 0.75 MMOL), 5-amino-2'- bromo-biphenyl-3-carboxylic acid methyl ester (216 mg, 0.71 MMOL), potassium carbonate (828 mg, 6 MMOL) and tetrakis (TRIPHENYLPHOSPHINE) PALLADIUM (0) (79 mg, 0. 068MOL) in 1: 1 toluene/ethanol (8 ml) was stirred and heated at 90C under nitrogen for 2 hours. After cooling the mixture was diluted with diethyl ether and water and the organic phase dried (MGS04) and evaporated to dryness. The residue was purified using Biotage with ethyl acetate/iso-hexane (1: 4) to yield the title compound as a pale yellow gum. (288 mg, 89%). 1H NMR (CDCl3) delta: 1.25 (3H, t, J=7Hz), 3.52 (2H, br s), 4.23 (2H, q, J=7Hz), 4.68 (2H, br s), 6.52 (1H, s), 6.63 (1H, d, J=9Hz), 7.00-7. 41 (13H, m). LC/MS t=3.93, [MH+] 458.2, 460.2.
  • 19
  • [ 690260-87-8 ]
  • [ 612832-83-4 ]
  • 2-benzyloxy-5"-fluoro-[1,1';2',1"]terphenyl-2"-carboxylic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; toluene; at 90℃; for 2h;Heating / reflux; A mixture OF 2'-BENZYLOXY-5'-CHLOROPHENYLBORONIC ACID (947mg, 3.61 MMOL), 2'-Bromo- biphenyl-2-carboxylic acid ethyl ester (1. 0g, 3.28 MMOL), potassium carbonate (3.39g, 24. 6MMOL), and tetrakis (triphenylphosphine) palladium (0) (379mg, 0. 32MMOL) in1 : 1 TOLUENE/ETHANOL (40ML) was stirred and heated at 90C under nitrogen for 2 hours. After cooling the mixture was diluted with diethyl ether and water. The organic phase was dried and evaporated. The residue was chromatographed eluting with DICHLOROMETHANE/ISO- hexane (1: 4 to 1: 1) to yield the title compound as a colourless gum (1. 28g, 88%). 1H NMR (CDCl3) delta: 0.98 (3H, br s), 4.09 (2H, br s), 4.77 (2H, m), 6.61 1H, d, J=9Hz), 7.0- 7.4 (14H, m), 7.69 (1 H, d, J=8Hz). LC/MS t=4.09.
  • 20
  • [ 4595-59-9 ]
  • [ 612832-83-4 ]
  • 5-[2-(benzyloxy)-3-chlorophenyl]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; for 48h;Heating / reflux; A mixture of the product from step (ii) (0.2g), 5-BROMOPYRIMIDINE (0.16g), sodium carbonate (0.21g) and tetrakistriphenylphosphine palladium (0) (0. 05g) in dioxane (6ML) was heated under reflux for 48h. The mixture was partitioned between EtOAc and water, the organics separated, dried, and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 20% EtOAc/isohexane. Yield 0.283g. MS: APCI (+ve): 297/9 (M+1)
  • 21
  • [ 4858-85-9 ]
  • [ 612832-83-4 ]
  • [ 850913-58-5 ]
YieldReaction ConditionsOperation in experiment
80% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 20℃; for 20h;Heating / reflux; a) 2-[2Benzvloxv)-5-chlorol-3-chloro-pvrazine 2, 3-Dichloropyrazine (255mg, 1.71 mmol), 2- (benzyloxy)-5-chloro-phenylboronic acid (450mg, 1.71 mmol) and sodium carbonate (139mg) were stirred in DME (ethylene glycol dimethyl ether) -water (1: 1,10 mL) under nitrogen for 20 minutes, then tetrakis (triphenylphoshine) palladium (0) (100mg) was added and the mixture heated at reflux for 20 hours. Upon cooling, saturated ammonium chloride was added and the resultant mixture was extracted with DCM (x 2). The combined extracts were dried (MgS04), filtered and evaporated. The residue was chromatographed on silica gel with with cyclohexane containing ethyl acetate (5-100%) to yield the title compound (448mg, 80%). LC/MS Rt = 3.47 min, [MH+] 331.
  • 22
  • [ 149418-41-7 ]
  • [ 612832-83-4 ]
  • [ 850913-59-6 ]
YieldReaction ConditionsOperation in experiment
With triphenyl-arsane; silver(l) oxide;dichloro bis(acetonitrile) palladium(II); In tetrahydrofuran; at 50℃; for 16h; a) 3-Bromo-4-f2-(benzvloxv)-5-chloro-phenvll-2 (5H) -furanone 2- (Benzyloxy)-5-chloro-phenylboronic acid (1.58g, 6mmol) and 3,4-dibromo-2 (5H) - furanone (1.21g, 5mmol) were dissolved in tetrahydrofuran (50ml) under nitrogen and bis (acetonitrile) dichloropalladium (ll) (130mg, 0. 5mmol), triphenylarsine (310mg, 1mmol) and silver (II) oxide (3.48g, 15mmol) added. The mixture was stirred and heated to 50C for 16 hours. Ethyl acetate (125ml) was added and the mixture filtered through a pad of Kieselguhr. The filtrate was washed with water (x2), dried (MgSO4) and evaporated. The residue was purified by chromatography on silica gel, eluting with 5-20% ethyl acetate in isohexane. The product was triturated with diethyl ether/isohexane and the solid filtered and dried in vacuo to give the title compound. (738mg). 'H NMR (CDCI3) 8H : 5.09 (2H, s), 5.16 (2H, s), 7.00 (1H, d, J=9Hz), 7.34-7. 42 (6H, m), 7.79 (1 H, d, J=2.5Hz).
  • 23
  • [ 850913-60-9 ]
  • [ 612832-83-4 ]
  • [ 850913-61-0 ]
YieldReaction ConditionsOperation in experiment
With triphenyl-arsane; silver(l) oxide;dichloro bis(acetonitrile) palladium(II); In tetrahydrofuran; at 60℃; for 32h; b) 3-{3-[2-(Benzyloxy)-5-chloro-phenyl]-2-oxo-2,5-dihydro-furan-4-yl}-benzoic acid tert- butvi ester 3- (3-bromo-2-oxo-2, 5-dihydrofuran-4-yl)-benzoic acid ter-butyl ester (60mg, 0. 177mmol) and 2- (benzyloxy)-5-chlorophenylboronic acid (56mg, 0. 212mol) were dissolved in tetrahydrofuran (2ml) under nitrogen and bis (acetonitrile) dichloropalladium (ll) (5mg, 0. 0177mmol), triphenylarsine (9mg, 0. 035mmol) and silver (II) oxide (103mg, 0. 531mmol) added. The mixture was stirred and heated to 60C for 16 hours. The mixture was then filtered through a pad of Kieselguhr and washed with ethyl acetate. The filtrate was evaporated. The residue was dissolved in tetrahydrofuran (2ml) under nitrogen and 2- (benzyloxy)-5-chlorophenylboronic acid (28mg, 0. 106mol). Bis (acetonitrile) dichloropalladium (II) (2.5mg, 0. 0088mmol), triphenylarsine (4.5mg, 0. 018mmol) and silver (II) oxide (52mg, 0. 265mol) added. The mixture was stirred and heated to 60C for 16 hours. Ethyl acetate (10ml) was added and the mixture filtered through a pad of Kieselguhr The filtrate was washed with water (x2), dried (MgS04) and evaporated. The residue was purified by chromatography on silica gel, eluting with 5-15% ethyl acetate in isohexane to give the title compound. (37mg). LC/MS Rt 3.90 min, [MH-] 475,477.
  • 24
  • [ 850913-62-1 ]
  • [ 612832-83-4 ]
  • [ 850913-63-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 16h; 3-{3-[2-(Benzyloxy)-5-chloro-phenyl]-pyridin-4-yl}-benzoic acid ethyl este A mixture of ethyl 3- (3-bromopyridin-4-yl) benzoate (156mg, 0.51 mmol), 2- (benzyloxy)-5- chlorophenylboronic acid (157mg, 0.6 mmol), potassium carbonate (568mg, 4.11 mmol) and tetrakis (triphenylphosphine) palladium (0) (66mg, 0.057 mmol) was stirred and heated at 90C in 1: 1 toluene/ethanol (5 ml) for 16 hours then cooled to room temperature and diluted with ether/water. The organic phase was dried (magnesium sulphate), evaporated and purified by chromatography on silica eluting with ethyl acetate/iso-hexane (1: 3) to give the title compound (179mg) as a colourless gum. LC/MS t=3.79, [MH+] 444.0, 446.0.
  • 25
  • [ 49676-92-8 ]
  • [ 612832-83-4 ]
  • [ 850897-38-0 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 4h; 2- (2-Bromo-1-cvclohexen-1-vl)-4-chloro-1-f (ahenvlmethvl) oxvlbenzene; A mixture of <strong>[612832-83-4]2-benzyloxy-5-chlorophenylboronic acid</strong> (2. 983g, 11.36 mmol), 1,2- dibromocyclohexene (10. 91g, 45.46 mmol), potassium carbonate (13. 8g, 100 mmol) and tetrakis (triphenylphosphine) palladium (0) (1.158g, 1 mmol) in 1: 1 toluene/ethanol (250m1) was stirred and heated at 90 C under nitrogen for 4 hours. After cooling the mixture was diluted with diethyl ether and water and the organic layer separated, dried (magnesium sulphate) and evaporated to dryness. The residue was chromatographed on silica eluting with ethyl acetate/iso-hexane (1: 49) then rechromatographed eluting with dichloromethane/iso-hexane (1: 9) and recrystallised from iso-hexane to give 638mg of white crystals. 'H NMR (d6DMSO) 8 : 1.55-1. 80 (m, 4H), 2.12-2. 22 (m, 1H), 2.30-2. 41 (m, 1H), 2.51-2. 60 (m, 2H), 5. 13 (s, 2H), 7.07 (d, 1H), 7.10 (d, 1H), 7.28-7. 43 (m, 6H).
  • 26
  • [ 75415-78-0 ]
  • [ 612832-83-4 ]
  • [ 612833-47-3 ]
YieldReaction ConditionsOperation in experiment
62% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 2h; General Procedure C General Procedure C (i) 1-Bromo-2- (2-benzyloxy-5-chlorophenyl) cyclopentene A mixture of 1, 2-dibromocyclopentene (1.72 g, 7.6 mmol), 2-benzyloxy-5- chlorophenylboronic acid (500 mg, 1.9 mmol), potassium carbonate (2.1 g, 15.2 mmol) and tetrakis (triphenyl phosphine) palladium (0) (220 mg, 0.19 mmol) was stirred and heated in 1: 1 toluene/ethanol (15 ml) at 90C under nitrogen for 2 hours. After cooling the mixture was diluted with diethyl ether/water and the organic phase dried (magnesium sulphate), evaporated to dryness and the residue purified by chromatography on silica ( 2% ethyl acetate in iso-hexane then 10% dichloromethane in iso-hexane) to yield the title compound as a white solid (427 mg, 62%). 'H NMR (CDCI3) 6 : 1.99-2. 07 (2H, m), 2.67-2. 72 (2H, m), 2.76-2. 81 (2H, m), 5.06 (2H, s), 6.85 (1H, d, J=9Hz), 7.17-7. 38 (7H, m).
  • 27
  • [ 612833-44-0 ]
  • [ 612832-83-4 ]
  • 5-{2-[5-chloro-2-benzyloxyphenyl]cyclopenten-1-enyl}-2-methylbenzoic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 90℃; for 2h; General Procedure B (iii) 5-{2-[5-chloro-2-benzyloxyphenyl]cyclopenten-1-enyl}-2-methylbenzoic acid ethyl ester (5-chloro-2-benzyloxyphenyl) boronic acid (150 mg, 0.5 mmol), Pd (0) [PPh3] 4 (25mg, 0. 021mol), potassium carbonate (483mg, 3.36 mmol) and 3-(2-bromo-cyclopent-1-enyl)- 6-methylbenzoic acid ethyl ester (130 mg, 0.42 mmol) in toluene-ethanol (1: 1 10 mL) were stirred at 90C, under nitrogen, for 2hrs. Upon cooling, the reaction mixture was poured into water and extracted with ethyl acetate (3x20mL). The combined organic layers were dried (MgS04), filtered and concentrated. The residue was purified on a Biotage using 5% of ethyl acetate in iso-hexane to give the required product as white solid(114 mg, 61%). 'HNMR (CDCI3) : 1.27 (3H, t, J=12Hz), 2.01-2. 08 (2H, m), 2.51 (3H, s), 2.83 (2H, t, J=6Hz), 2.90 (2H, t, J=6Hz), 4.94 (2H, s), 6.80 (1 H, d, J=Hz), 6.97-7. 70 (9H, m), 7.70 (1 H, s). LC/MS; Rt=4.22 [M+H] 447 (1 Cl)
  • 28
  • [ 612832-85-6 ]
  • [ 612832-83-4 ]
  • [ 612832-86-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; for 17h;Heating / reflux; b) 3-42-f5-chloro-2- (benzyloxy)-phenyll-cyclopent-1-enyl)-benzoic acid ethyl ester 3-(2-Bromocyclopent-1-enyl)-benzoic acid ethyl ester (0.148g, 0.0005 mol), Pd (O) [PPh3] 4 (30mg), potassium carbonate (0. 2g) and (2-benzyloxy-5-chlorophenyl) boronic acid (150mg, 0.0005 mol) in dimethoxyethane (5mL) were refluxed for 17h under nitrogen. The reaction mixture was then filtered through Kieselgur and evaporated down to an oil. Purification was carried out on a Water's separation pack (10g) with dichloromethane/iso- hexane giving the product (85mg). 'H NMR (400MHz, CDCI3) 1.31 (3H, t, J=7Hz), 2.01-2. 12 (2H, m), 2.81-2. 88 (4H, m's), 4.28 (2H, q, J=8Hz), 4.93 (2H, s), 6.81 (1 H, d, J=8Hz), 7. 02, (1H, d, J=2Hz), 7.10-7. 33 (8H, m's excess), 7.76-7. 86 (2H, m). LC/MS rt 4. 21, [MH+] 433.
  • 29
  • [ 76-09-5 ]
  • [ 612832-83-4 ]
  • [ 779331-27-0 ]
YieldReaction ConditionsOperation in experiment
In diethyl ether; for 48h;Molecular sieve; The sub-title compound was prepared from the product of step b) (5 g), pinacol (2.7 g)in anhydrous diethyl ether (200 ml). The reagents were stirred under nitrogsn overnight. Afurther 1.2 g of pinacol and molecular seives were added and stirred overnight. The reacionmixture was washed with water, dried (MgSO^ and concentrated in vacua to give the sub- title compound (5.6 g).^NMRDMSO-de: 8 7.27-7.64 (m, 7H), 6.85 (d, IH), 5.09 (s, 2H), 1.36 (s, 12H) Pinacol (3.24 g) was added to a solution of [5-chloro-2-(phenylmethoxy)phenyl]-boronic acid (6 g) in diethyl ether, and stirred for 24 h. 4A molecular sieves and pinacol (1.5g) were added, stirred for a further 24 h. The sieves were filtered and the filtrate was washedwith water and brine, then dried (MgSCU) and concentrated in vacuo. Yield 6.8 g..H NMR DMSO-D6: 8 7.6-7.25 (7H, m), 7.08 (1H, d), 5.13 (2H, s), 1.32 (12H, s)
  • 30
  • 4-[[4-bromo-2-(trifluoromethyl)phenyl]sulfonyl]morpholine [ No CAS ]
  • [ 612832-83-4 ]
  • [ 877383-39-6 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; methanol; at 85℃; for 16h; A mixture of the product of step a) (450 mg) and [5-chloro-2-(phenylmethoxy)phenyl]boronic acid (351 mg), sodium carbonate (277 mg) and Pd(dppf)Cl2(93 mg) in dioxan (3 ml) and methanol (0.5 ml) was heated at 85 C for 16 h. Water wasadded and the mixture was extracted with ether (three times), the organic extracts were dried(MgSC>4), evaporated and purified by chromatography (silica, petrol - ether as eluent) to givethe sub-title compound (538 mg).M.p. 118-9C..H NMR CDC13: 5 8.13-8.04 (2H, m), 7.83 (1H, dd), 7.37-7.26 (7H, m), 7.04 (1H, d), 5.09(2H,s), 3.74 (4H,t), 3.25 (4H,t).
  • 31
  • [ 23038-36-0 ]
  • [ 612832-83-4 ]
  • [ 933062-47-6 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 80℃; for 16h; [5-Chloro-4'-(phenylsulfonyl)biphenvI-2-vnoxy>acetic acid() 2'-(BenzyloxgammaV5'-chlorobiphengammal-4-gammal phenyl sulfone 5-Chloro-2-(phenylmethoxy)phenyl]-boronic acid (prepared by the method ofWO2004089885A1) (0.5g) in dioxan (20ml) was treated with l-bromo-4-(phenylsulfonyl)benzene (0.57g) prepared by the method used in JACS (1952), 74, 394-7.Sodium carbonate (0.4Og) andpalladium(diphenylrhohosphinoferrocene) dichloride (0.070g) were added and the mixture heated to 8O0C for 16 hours. The mixture was diluted with water, extracted with ethyl acetate, dried and evaporated under reduced pressure to give an oil. The oil was purified by chromatography on silica eluting with isohexane/diethylether 2: 1 to give the sub-title compound as a white solid, yield 0.9g.1H NMR CDCl3: delta 8.00-7.92 (4H,m), 7,67-7.49 (5H, m), 7.30-7.19 (7H, m), 7,02-6;95-(lH, d), 5.08 (2H, s).
  • 32
  • [ 960235-24-9 ]
  • [ 612832-83-4 ]
  • C20H18ClNO3S [ No CAS ]
  • 33
  • [ 62290-17-9 ]
  • [ 612832-83-4 ]
  • C23H21ClO3 [ No CAS ]
  • 34
  • [ 28188-41-2 ]
  • [ 612832-83-4 ]
  • [ 847148-94-1 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃; for 5h; A mixture of <strong>[612832-83-4]2-benzyloxy-5-chlorophenylboronic acid</strong> (2. 1G), 3-cyanobenzyl bromide (1.57g), sodium carbonate (1.7g) and tetrakis (triphenylphosphine) palladium (0) (0.46g) in ethylene glycol dimethyl ether (30ML) was heated at 80C for 5H. The mixture was cooled, partitioned between WATER/DIETHYLETHER, the organics separated, dried and evaporated under reduced pressure. The residue was purified by chromatography on silica eluting with 5% ethylacetate/isohexane, yield 0.53g. H NMR DMSO-D6 : 8 7.68-7. 24 (11H, m); 7.08 (1H, d); 5.10 (2H, s); 3.97 (2H, s)
  • 35
  • [ 7700-27-8 ]
  • [ 612832-83-4 ]
 

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