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Chemical Structure| 874219-45-1 Chemical Structure| 874219-45-1

Structure of 874219-45-1

Chemical Structure| 874219-45-1

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Product Details of [ 874219-45-1 ]

CAS No. :874219-45-1
Formula : C8H8BClO4
M.W : 214.41
SMILES Code : ClC1=C(C=C(C=C1)B(O)O)C(=O)OC
MDL No. :MFCD06801690
InChI Key :YEPWHDGFBVDINZ-UHFFFAOYSA-N
Pubchem ID :23005334

Safety of [ 874219-45-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 874219-45-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 52.56
TPSA ?

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

66.76 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

1.31
Log Po/w (WLOGP)?

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

-0.19
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.

0.79
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

-0.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.34

Water Solubility

Log S (ESOL):?

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

-2.11
Solubility 1.65 mg/ml ; 0.0077 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.

-2.31
Solubility 1.04 mg/ml ; 0.00487 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

-1.99
Solubility 2.2 mg/ml ; 0.0103 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

No
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.

-6.68 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<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)

1.99

Application In Synthesis of [ 874219-45-1 ]

* 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 [ 874219-45-1 ]

[ 874219-45-1 ] Synthesis Path-Downstream   1~18

  • 1
  • [ 19755-53-4 ]
  • [ 874219-45-1 ]
  • [ 1143025-92-6 ]
YieldReaction ConditionsOperation in experiment
61.0% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In ethanol; toluene; at 100.0℃; for 6.0h;Microwave irradiation; Intermediate 112 : methyl 2-chloro-5-(3-nitropyridin-2-yl)benzoate; 2-Bromo-3-nitropyridine (1.25 g, 6.16 mmol), 4-chloro-3- (methoxycarbonyl)phenylboronic acid (1.32 g, 6.16 mmol), tetrakis(triphenylphosphine)palladium(0) (0.36 g, 0.310 mmol) and sodium carbonate (0.653 g, 6.16 mmol) were suspended in toluene (15 mL) and ethanol (15.0 mL) and sealed into a microwave tube. The reaction was heated to 100 0C for 5 hours in the microwave reactor and cooled to RT. The reaction was incomplete and further 2-bromo-3- nitropyridine (0.625 g, 3.08 mmol) was added and the mixture was heated to 100 0C for a further 1 hour. The reaction mixture was filtered through celite, rinsed through with ethyl acetate (25 mL) and washed with water (1 x 50 mL) then brine (1 x 50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-chloro-5-(3- nitropyridin-2-yl)benzoate (1.100 g, 61.0 %) as a yellow solid, m/z (ESI+) (M+H)+ = 293.25; HPLC tR = 2.31 min. 1H NMR (400 MHz, CDCl3) delta 3.94 (3H, s), 7.48 - 7.52 (IH, m), 7.54 - 7.56 (IH, m), 7.57 - 7.60 (IH, m), 8.10 - 8.11 (IH, m), 8.21 - 8.23 (IH, m), 8.87 - 8.89 (IH, m).
  • 2
  • [ 874219-45-1 ]
  • [ 4595-60-2 ]
  • [ 1143024-54-7 ]
YieldReaction ConditionsOperation in experiment
42% palladium diacetate; triphenylphosphine; In tetrahydrofuran; at 65.0℃; Intermediate 5: Methyl 2-chloro-5-(pyrimidin-2-yl)benzoate; A mixture of 2-bromopyrimidine (2.8 g, 17.63 mmol), <strong>[874219-45-1]4-chloro-3-(methoxycarbonyl)phenylboronic acid</strong> (4.2 g, 19.59 mmol), palladium acetate (0.22 g, 0.98 mmol) and triphenylphosphine (1.028 g, 3.92 mmol) in THF (80 mL) was heated at 65 0C overnight, then the reaction mixture was cooled, filtered through Celite and concentrated in vacuo. The residue was partitioned between EtOAc (200 mL) and saturated brine (200 mL) and the organic phase was dried, concentrated in vacuo, and then the residue was purified by chromatography on silica gel eluting with EtOAc/isohexane (0 - 50%) to give the title compound as a white solid (2.0 g, 42%): MS 249.
  • 3
  • [ 874219-45-1 ]
  • [ 1071958-95-6 ]
  • C29H31Cl2NO6 [ No CAS ]
  • 4
  • [ 874219-45-1 ]
  • [ 121489-29-0 ]
  • [ 603123-95-1 ]
  • 5
  • [ 874219-45-1 ]
  • [ 1326714-17-3 ]
  • 5-{7-amino-4-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]furo[2,3-c]pyridin-2-yl}-2-chlorobenzoic acid hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% Step A: 5-{7-amino-4-M -(piperidin-4-yl V 1 H-pyrazol-4-yllfuror2.3-clpyridin-2-yl)-2- chlorobenzoic acid hydrochlorideA suspension of 1-{4-[4-(7-amino-2-chlorofuro[2,3-c]pyridin-4-yl)-1 H-pyrazol-1 - yl]piperidin-1-yl}ethanone (125 mg, 0.347 mmol), <strong>[874219-45-1]4-chloro-3-(methoxycarbonyl)phenylboronic acid</strong> (89.4 mg, 0.417 mmol), and Pd(PPh3)4 (40.1 mg, 0.0347 mmol) in 1.0 M aqueous sodium carbonate (1 .74 mL, 1.74 mmol) and 1 ,4-dioxane (1.63 mL) was heated to 120 C in a microwave for 30 min. The reaction mixture was then diluted with ethyl acetate (10 mL) and acidified with aqueous 1 N hydrochloric acid (5 mL), causing formation of a precipitate. The precipitate was collected by vacuum filtration and then triturated from DMSO and methanol (10 mL, -1 :10) to afford 55 mg (29%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): delta 8.45 (d, J = 1.5 Hz, 1 H), 8.29 (s, 1 H), 8.22 (dd, J = 1.8, 8.3 Hz, 1 H), 8.00 (d, J = 8.1 Hz, 2H), 7.91 (s, 1 H), 7.75 (d, J = 8.6 Hz, 1 H), 6.56 (br s, 2H), 4.61 - 4.30 (m, 2H), 3.94 (br s, 1 H), 3.24 (br s, 1 H), 2.74 (br s, 1 H), 2.26 - 1.63 (m, 7H); MS (ESI): 480.10 [M+H]+; HPLC tR = 2.35 min (ZQ3, polar_4min).
  • 6
  • [ 905281-79-0 ]
  • [ 874219-45-1 ]
  • [ 1314264-36-2 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate;bis-triphenylphosphine-palladium(II) chloride; In 1,4-dioxane; water; at 150.0℃; for 0.5h;Microwave irradiation; 00242] Step 2: A microwave vessel was charged with 2-(4-bromo-3-pyridin-4-yl- pyrazol-l-yl)-ethanol (180 mg, 0.669 mmol), <strong>[874219-45-1]4-chloro-3-(methoxycarbonyl)phenylboronic acid</strong> (172 mg, 0.803 mmol), PdCl2(PPh3)2 (27.3 mg, 0.033 mmol) under a nitrogen atmosphere. 1 ,4-Dioxane (3.5 mL) and saturated aqueous sodium bicarbonate (1.5 mL) were added. The vessel was capped and microwaved at 150C for 30 min. in a Biotage Initiator microwave instrument. The mixture was extracted with ethylacetate, dried over MgS04 and adsorbed onto silica gel. The methyl ester product was purfied bychromatography using a gradient of 50-100% Hexanes/ethylacetate to afford 54 mg.
  • 7
  • [ 874219-45-1 ]
  • [ 1314264-22-6 ]
  • [ 1314264-18-0 ]
YieldReaction ConditionsOperation in experiment
44% [00223] Step 2: 2-Chloro-5-(2-phenyl-4-(2-methoxypyridin-4-yl)-lH-imidazol-5- yl)benzoic acid. A microwave vessel was charged with 2-phenyl-4-bromo-5-(2- methoxypyridin-4-yl)-lH-imidazole (55 mg, 0.167 mmol), 4-chloro-3- methoxycarbonylphenylboronic acid (39 mg, 0.183 mmol), PdCl2(PPh3)2 (6 mg, 0.008 mmol), and potassium carbonate (138 mg, 1 mmol) under nitrogen atmosphere. Degassed DME (1.6 mL) and water (0.4 mL) were added. The vessel was capped and microwaved at 150C for 30 min. in a Biotage Initiator microwave instrument. A IN aqueous solution of KOH (3 mL) was added and the mixture was further stirred overnight. The reaction mixture was filtered through celite and the filtrate was extracted with EtOAc (3x). The aqueous layer was isolated and acidified to pH 4.5 with concentrated HCl. The resulting precipitate was filtered, washed with water, and dried in vacuo to give 30 mg of the title compound as a light green solid (44% yield, two imidazole tautomers): main tautomer 1H NMR (DMSO- d6, ppm) delta 3.86 (s, 3H), 6.94 (broad s, 1H), 7.12 (d, 1H), 7.45 (t, 1H), 7.51-7.66 (m, 4H), 7.97-8.22 (m, 4H), 13.0 (broad s, 1H), 13.5 (broad s, 1H); [M+H+] m/z 406.
  • 8
  • [ 874219-45-1 ]
  • 6-((6-bromo-8-fluoroimidazo[1,2-a]pyridin-3-yl)methyl)quinoline [ No CAS ]
  • methyl 2-chloro-5-(8-fluoro-3-(quinolin-6-ylmethyl)imidazo[1,2-a]pyridin-6-yl)benzoate [ No CAS ]
  • 9
  • [ 874219-45-1 ]
  • 5-(6-amino-3-chloro-5-fluoropyridin-2-yl)-2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)benzamide [ No CAS ]
  • 10
  • [ 874219-45-1 ]
  • 5-(6-((tert-butoxycarbonyl)amino)-3-chloro-5-fluoropyridin-2-yl)-2-chlorobenzoic acid [ No CAS ]
  • 11
  • [ 874219-45-1 ]
  • methyl 5-(6-((tert-butoxycarbonyl)amino)-3-chloro-5-fluoropyridin-2-yl)-2-chlorobenzoate [ No CAS ]
  • 12
  • [ 874219-45-1 ]
  • methyl 5-(6-amino-3-chloro-5-fluoropyridin-2-yl)-2-chlorobenzoate [ No CAS ]
  • 13
  • [ 874219-45-1 ]
  • 2-amino-6-chloro-3-fluoropyridine [ No CAS ]
  • methyl 5-(6-amino-5-fluoropyridin-2-yl)-2-chlorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100.0℃; for 2.0h; To a degassed solution of <strong>[874219-45-1](4-chloro-3-(methoxycarbonyl)phenyl)boronic acid</strong> (1.67 g, 7.79 mmol), 6-chloro-3-fluoropyridin-2-amine (1.51 g, 8.18 mmol), potassium carbonate (3.25 g, 23.4 mmol) and water (20 mL) in dioxane (95 mL) was added [1 ,1 - bis(diphenylphosphino)ferrocene] dichloropalladium(ll) (615 mg, 0.779 mmol). The reaction was stirred at 100C for 2 hours. The reaction was cooled and diluted with water (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (2 x 80mL), and the combined organic layers were washed with brine (100 mL), dried over MgS04 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 20% ethyl acetate in heptanes to afford the title compound (875 mg, 40%). 1 H NMR (400MHz, CDCI3): delta ppm 3.96 (s, 3H), 4.68 (br s, 2H), 7.06 (dd, 1 H), 7.28 (m, 1 H), 7.49 (d, 1 H), 7.95 (dd, 1 H), 8.36 (d, 1 H).
  • 14
  • [ 874219-45-1 ]
  • 7-bromo-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine [ No CAS ]
  • methyl 5-(4-amino-5-(1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-chlorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With tetrakis(triphenylphosphine) palladium(0); tripotassium phosphate; In tetrahydrofuran; water; at 85.0℃; for 1.5h;Inert atmosphere; Sonication; Intermediate Ni, 7-bromo-5 -(1 -(tetrahydro-2H-pyran-4-yl)- 1H-pyrazol-5- yl)pyrrolo[2,1-J][1,2,4]triazin-4-amine, (0.325 g, 0.895 mmol), (4-chloro-3- (methoxycarbonyl)phenyl)boronic acid (0.326 g, 1.52 mmol) and K3P04 (0.76 mg, 3.58mmol) were combined in a 20 mL vial fitted with a septum and dissolved in a mixture of THF (6.51 mL) and water (0.65 mL). Argon was bubbled through the mixture while the vial was sonicated. Tetrakistriphenylphosphine palladium (0.1 g, 0.09 mmol) was added and the mixture was heated at 85 C. After 1.5 h, the reaction mixture was diluted with ethyl acetate (20 mL) and water (5 mL) and the layers were mixed and then separated (3times). The organic layers were mixed, dried over and concentrated. The residue was triturated with DCM, to obtain a white solid as the pure desired product (120 mg). Thefiltrate was concentrated and submitted for purification by silica gel column to obtain methyl 5-(4-amino-5-( 1 -(tetrahydro-2H-pyran-4-yl)- 1H-pyrazol-5-yl)pyrrolo [2,1 -J] [1,2,4]triazin-7-yl)-2-chlorobenzoate (323 mg, 0.7 13 mmol, 80% yield) as a pale yellow solid.
  • 15
  • [ 874219-45-1 ]
  • 1-[2,6-dimethyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]pyrrole [ No CAS ]
  • methyl 2-chloro-5-[1-[2,6-dimethyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]pyrrol-3-yl]benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
11099] 1.5 g (4.293 mmol) 1 -[2,6-dimethyl-4-[1 ,2,2,2-tet- rafluoro-1 -(trifluoromethyl)ethyl]phenyl]-pyrrole were dissolved in 60 ml of n-hexane, and 966 mg (4.3 mmol) of N-iodosuccinimide were added. Subsequently, the mixture was allowed to come to room temperature and stirred at room temperature for 6 days. Then a thrther 242 mg (1.1 mmol) of N-iodosuccinimide were added and the mixture was stirred at room temperature overnight. Subsequently, excess aqueous sodium hydrogen-sulphite solution and a little ethyl acetate were added. The organic phase was removed and first washed twice with aqueous sodium hydrogensulphite solution, then with saturated sodium chloride solution, dried with sodium sulphate and concentrated. For purification, chromatography was effected using a cartridge containing 120 g of silica gel and a gradient proceeding from pure cyclohexane to 95:5 cyclohexane/ethyl acetate (v/v). 453 mg of a mixture of 80% 1-[2,6-dimethyl-4-[1,2,2,2- tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl]-3-iodopyrrole and 16% 1 -[2,6-dimethyl-4-[1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]-2-iodopyrrole were obtained; jllOO] 998 mg (1.696 mmol) of a mixture of 80% 1-[2, 6-dimethyl-4-[1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl] phenyl]-3-iodopyrrole and 16% 1 -[2,6-dimethyl-4-[ 1,2,2,2- tetrafluoro-1 -(trifluoromethyl)ethyl]phenyl]-2-iodopyrroleand 364 mg (1.7 mmol) of 4-chloro-3-(methoxy-carbonyl)phenylboronic acid were initially charged in 10 ml of 2-propanol. Thereafter, the air was displaced by argon, and5.2 ml of 1 molar aqueous sodium hydrogencarbonatesolution and 98 mg (0.085 mmol) of tetrakis(triphenylphosphine)palladium(0) were added under argon. Subsequently, the mixture was heated to reflux for 3 hours. For workup, the mixture was cooled a little, then concentrated on a rotary evaporator under reduced pressure. The residue was partitioned between ethyl acetate and watet The organic phase was removed, washed with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. 1.57 g of crude methyl 2-chloro-5-[1-[2,6-dim- ethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]pyrrol-3-yl]benzoate were obtained.
1.5 g (4.293 mmol) l-[2,6-dimethyl-4-[i,2,2,2-tetrafluoro-l -(trifl^ dissolved in 60 ml of n-hexane, and 966 mg (4.3 mmol) of N-iodosuccinimide were added. Subsequently, the mixture was allowed to come to room temperature and stirred at room temperature for 6 days. Then a further 242 mg (1.1 mmol) of N-iodosuccinimide were added and the mixture was stirred at room temperature overnight. Subsequently, excess aqueous sodium hydrogen-sulphite solution and a little ethyl acetate were added. The organic phase was removed and first washed twice with aqueous sodium hydrogensulphite solution, then with saturated sodium chloride solution, dried with sodium sulphate and concentrated. For purification, chromatography was effected using a cartridge containing 120 g of silica gel and a gradient proceeding from pure cyclohexane to 95:5 eye lohexane/ ethyl acetate (v/v). 453 mg of a mixture of 80% 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl] -3 -iodopyrrole and 16% 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl]-2-iodopyrroie were obtained. 998 mg (1.696 mmol) of a mixture of 80% 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl] -3 -iodopyrrole and 16% 1 -[2,6-dimethyl-4-[ i ,2,2,2-tetrafluoro- 1 - (trifluoromethyl)ethyl]phenyl]-2-iodopyrrole and 364 mg (1.7 mmol) of 4-chloro-3-(methoxy- c arbony l)pheny lboronic acid were initially charged in 10 ml of 2-propanol. Thereafter, the air was displaced by argon, and 5.2 ml of 1 molar aqueous sodium hydrogencarbonate solution and 98 mg (0.085 mmol) of tetrakis(triphenylphosphine)palladium(0) were added under argon. Subsequently, the mixture was heated to reflux for 3 hours. For workup, the mixture was cooled a little, then concentrated on a rotary evaporator under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic phase was removed, washed with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. 1.57 g of crude methyl 2-chloro-5-[l-[2,6- dimethyl-4-[l, 2,2,2 -tetrafluoro-l -(trifluoromethyl)ethyl]phenyl]pyrrol-3-yl]benzoate were obtained.
  • 16
  • [ 874219-45-1 ]
  • 3-[2,6-dimethyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole [ No CAS ]
  • methyl 2-chloro-5-[3-[2,6-dimethyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]pyrazol-1-yl]benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
628 mg With pyridine; copper diacetate; In dichloromethane; at 20.0℃; for 20.0h;Molecular sieve; 10967] 23 ml of dichloromethane, 353 mg (4.46 mmol) of pyridine, 609mg (3.35 mmol) of copper(II) acetate, 958mg (4.46 mmol) of 3-carboxymethyl-4-chlorophenylboronic acid and 760 mg (2.23 mmol) of (3-[2,6-dimethyl-4-[1,2,2, 2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl] -1 H-pyrazolewere initially charged and then 1.1 g of freshly ground 3 A molecular sieve were added. The mixture was then stirred at room temperature for 20 hours. For workup, the mixture was filtered through a layer of kieselguhr and washed through with dichloromethane. The filtrate was concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected first using a cartridge containing 40 g of silica gel with a gradient in cyclohexane/ethyl acetate of 95:5 to 75:25 (v/v). The product-containing fractions were concentrated and chromatographed using a second cartridge containing 40 g of silica gel with toluene as eluent. After concentration, 628 mg of methyl 2-chloro-5- [3-[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro-1 -(trifluoromethyl) ethyl]phenyl]pyrazol-1 -yl]benzoate were obtained.
628 mg With pyridine; copper diacetate; In dichloromethane; at 20.0℃; for 20.0h;Molecular sieve; 23 ml of dichloromethane, 353 mg (4.46 mmol) of pyridine, 609 mg (3.35 mmol) of copper(II) acetate, 958 mg (4.46 mmol) of 3-carboxymethyl-4-chlorophenylboronic acid and 760 mg (2.23 mmol) of (3- [2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl] - 1 H-pyrazole were initially charged and then 1.1 g of freshly ground 3 A molecular sieve were added. The mixture was then stirred at room temperature for 20 hours. For workup, the mixture was filtered through a layer of kieselguhr and washed through with di chloromethane . The filtrate was concentrated on a rotary evaporator under reduced pressure. For purification, chromatography was effected first using a cartridge containing 40 g of silica gel with a gradient in cyclohexane/ ethyl acetate of 95:5 to 75:25 (v/v). The product-containing fractions were concentrated and chromatographed using a second cartridge containing 40 g of silica gel with toluene as eluent. After concentration, 628 mg of methyl 2 -chloro-5-[3-[2,6-dimethyl-4-[ 1,2,2,2- tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]pyrazol-l -yljbenzoate were obtained.
  • 17
  • [ 874219-45-1 ]
  • 1-[2,6-dimethyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-4-iodopyrazole [ No CAS ]
  • methyl 2-chloro-5-[1-[2,6-dimethyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]pyrazol-4-yl]benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
151 mg With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In isopropyl alcohol;Reflux; 10980] A 100 ml flask was initially charged with 280 mg (0.6 mmol) of 1 -[2,6-dimethyl-4-[1 ,2,2,2-tetrafluoro-1 -(tnfluoromethyl)ethyl]phenyl]-4-iodopyrazole and 0.129 g (0.60 mmol) of [4-chloro-3-(methoxycarbonyl)phenyl]bo- ronic acid in 21 ml of isopropanol, and lastly 1.84 ml (1.84 mmol) of degassed 1 molar sodium hydrogencarbonate solution were added. 0.035 g (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) was added. Then the mixture was heated to reflux. For workup, the mixture was concentrated on a rotary evaporator, and the residue was partitioned between water and ethyl acetate. The organic phase was removed, washed once with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. The residue was purified by chromatography with silica gel by means of a gradient from 90:10 to 70:30 (v/v) in cyclohexane/ethyl acetate, and gave 151 mg of methyl 2-chloro-5-[ 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]pyrazol-4-yl]benzoate.
151 mg With tetrakis(triphenylphosphine) palladium(0); sodium hydrogencarbonate; In isopropyl alcohol;Reflux; A 100 ml flask was initially charged with 280 mg (0.6 mmol) of 1 -[2,6-dimethyl-4-[ 1 ,2,2,2 -tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl] -4-iodopyrazole and 0.129 g (0.60 mmol) of [4-chloro-3- (methoxycarbonyl)phenyl]boronic acid in 21 ml of isopropanol, and lastly 1.84 ml (1.84 mmol) of degassed 1 molar sodium hydrogenc arbonate solution were added. 0.035 g (0.03 mmol) of tetrakis(triphenylphosphine)palladium(0) was added. Then the mixture was heated to reflux. For workup, the mixture was concentrated on a rotary evaporator, and the residue was partitioned between water and ethyl acetate. The organic phase was removed, washed once with saturated sodium chloride solution and concentrated on a rotary evaporator under reduced pressure. The residue was purified by chromatography with silica gel by means of a gradient from 90: 10 to 70:30 (v/'v) in eye lohexane/ethy 1 acetate, and gave 151 mg of methyl 2-chloro-5-[ 1 -[2,6-dimethyl-4-[ 1 ,2,2,2-tetrafluoro-l - (trifluoromethyl)ethyl]phenyl]pyrazol-4-yl]benzoate.
  • 18
  • [ 874219-45-1 ]
  • 5-(4-bromopyrazol-1-yl)-4-(difluoromethoxy)-1-methyl-3-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]pyrazole [ No CAS ]
  • methyl 2-chloro-5-[1-[4-(difluoromethoxy)-2-methyl-5-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]pyrazol-3-yl]pyrazol-4-yl]benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; cesium fluoride; In 1,4-dioxane; at 120.0℃; for 0.5h;Inert atmosphere; Sealed tube; Microwave irradiation; A microwave tube was charged with 5-(4-bromopyrazol-1-yl)-4-(difluoromethoxy)-1-methyl-3-[1 , 2,2,2- tetrafluoro-1-(trifluoromethyl)ethyl]pyrazole (0.130 g), (4-chloro-3-methoxycarbonyl-phenyl)boronic acid (0.067 g), Pd(dppf)2Cl2 (4.2 mg), anhydrous cesium fluoride (0.094 g) and anhydrous dioxane (1 mL). The tube was purched with argon, sealed up and heated in a microwave reacter to 120 C for 30 min. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was consecutively washed with water and brine, dried over magnesium sulfate and evaporated. The crude product was purified by flash chromatography (silica, cyclohexane / gradient of ethyl acetate from 0 to10%). LC-MS (Method A): tR = 1.22 min, m/z = 549 [M-1], 551 [M+1].
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bouveault-Blanc Reduction • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Ester Cleavage • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions with Organometallic Reagents • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

Related Functional Groups of
[ 874219-45-1 ]

Organoborons

Chemical Structure| 874219-46-2

A429740 [874219-46-2]

(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 913835-32-2

A420086 [913835-32-2]

5-Borono-2-chlorobenzoic acid

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Chemical Structure| 603122-80-1

A203645 [603122-80-1]

(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 603122-82-3

A206583 [603122-82-3]

(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 913835-75-3

A105916 [913835-75-3]

2-Chloro-5-carboxyphenylboronic acid

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Aryls

Chemical Structure| 874219-46-2

A429740 [874219-46-2]

(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 913835-32-2

A420086 [913835-32-2]

5-Borono-2-chlorobenzoic acid

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Chemical Structure| 603122-80-1

A203645 [603122-80-1]

(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 603122-82-3

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(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 913835-75-3

A105916 [913835-75-3]

2-Chloro-5-carboxyphenylboronic acid

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Chlorides

Chemical Structure| 874219-46-2

A429740 [874219-46-2]

(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 913835-32-2

A420086 [913835-32-2]

5-Borono-2-chlorobenzoic acid

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Chemical Structure| 603122-80-1

A203645 [603122-80-1]

(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 603122-82-3

A206583 [603122-82-3]

(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 913835-75-3

A105916 [913835-75-3]

2-Chloro-5-carboxyphenylboronic acid

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Esters

Chemical Structure| 874219-46-2

A429740 [874219-46-2]

(4-Chloro-3-(ethoxycarbonyl)phenyl)boronic acid

Similarity: 0.97

Chemical Structure| 603122-80-1

A203645 [603122-80-1]

(2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

Similarity: 0.89

Chemical Structure| 603122-82-3

A206583 [603122-82-3]

(3-Chloro-4-(methoxycarbonyl)phenyl)boronic acid

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Chemical Structure| 99769-19-4

A225713 [99769-19-4]

3-(Methoxycarbonyl)phenylboronic acid

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Chemical Structure| 177735-55-6

A256707 [177735-55-6]

(3,5-Bis(methoxycarbonyl)phenyl)boronic acid

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