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Chemical Structure| 5720-05-8 Chemical Structure| 5720-05-8

Structure of 4-Tolylboronic acid
CAS No.: 5720-05-8

Chemical Structure| 5720-05-8

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Synonyms: p-Tolylboronic acid

4.5 *For Research Use Only !

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Wen Ren ; Yuling Deng ; Jacob D. Ward ; Rebecca Vairin ; Ruoli Bai b ; Hashini I. Wanniarachchi , et al.

Abstract: The synthesis and evaluation of small-molecule inhibitors of tubulin polymerization remains a promising approach for the development of new therapeutic agents for cancer treatment. The natural products colchicine and combretastatin A-4 (CA4) inspired significant drug discovery campaigns targeting the colchicine site located on the beta-subunit of the tubulin heterodimer, but so far these efforts have not yielded an approved drug for cancer treatment in human patients. Interest in the colchicine site was enhanced by the discovery that a subset of colchicine site agents demonstrated dual functionality as both potent antiproliferative agents and effective vascular disrupting agents (VDAs). Our previous studies led to the discovery and development of a 2-aryl-3-aroyl-indole analogue (OXi8006) that inhibited tubulin polymerization and demonstrated low nM IC50 values against a variety of human cancer cell lines. A water-soluble phosphate prodrug salt (OXi8007), synthesized from OXi8006, displayed promising vascular disrupting activity in mouse models of cancer. To further extend structure-activity relationship correlations, a series of 6-aryl-3-aroyl-indole analogues was synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity against human cancer cell lines. Several structurally diverse molecules in this small library were strong inhibitors of tubulin polymerization and of MCF-7 and MDA-MB-231 human breast cancer cells. One of the most promising analogues (KGP591) caused significant G2/M arrest of MDA-MB-231 cells, disrupted microtubule structure and cell morphology in MDA-MB-231 cells, and demonstrated significant inhibition of MDA-MB-231 cell migration in a wound healing (scratch) assay. A phosphate prodrug salt, KGP618, synthesized from its parent phenolic precursor, KGP591, demonstrated significant reduction in bioluminescence signal when evaluated in vivo against an orthotopic model of kidney cancer (RENCA-luc) in BALB/c mice, indicative of efficacy. The most active compounds from this series offer promise as anticancer therapeutic agents.

Keywords: Inhibitors of tubulin polymerization ; Vascular disrupting agents ; synthesis ; Molecular docking ; Antiproliferative agents ; Inhibitors of cell migration

Purchased from AmBeed: ; ; ; ; ; 64-86-8 ; ; ; ; ; ; ; ; 4521-61-3 ; 4521-61-3 ; 87199-18-6 ; 64-86-8 ; 64-86-8 ; 128796-39-4 ; 5720-05-8 ; 64-86-8

Yuan, Gengyang ; Dhaynaut, Maeva ; Lan, Yu ; Guehl, Nicolas J. ; Huynh, Dalena ; Iyengar, Suhasini M. , et al.

Abstract: Metabotropic glutamate receptor 2 (mGluR2) is a therapeutic target for several neuropsychiatric disorders. An mGluR2 function in etiology could be unveiled by positron emission tomography (PET). In this regard, 5-(2-fluoro-4-[11C]methoxyphenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-7-carboxamide ([11C]13, [11C]mG2N001), a potent negative allosteric modulator (NAM), was developed to support this endeavor. [11C]13 was synthesized via the O-[11C]methylation of phenol 24 with a high molar activity of 212 ± 76 GBq/μmol (n = 5) and excellent radiochemical purity (>99%). PET imaging of [11C]13 in rats demonstrated its superior brain heterogeneity and reduced accumulation with pretreatment of mGluR2 NAMs, VU6001966 (9) and MNI-137 (26), the extent of which revealed a time-dependent drug effect of the blocking agents. In a nonhuman primate, [11C]13 selectively accumulated in mGluR2-rich regions and resulted in high-contrast brain images. Therefore, [11C]13 is a potential candidate for translational PET imaging of the mGluR2 function.

Hegde, Pooja V. ; Aragaw, Wassihun W. ; Cole, Malcolm S. ; Jachak, Gorakhnath ; Ragunathan, Priya ; Sharma, Sachin , et al.

Abstract: Tuberculosis (TB) remains a leading cause of infectious disease-related mortality and morbidity. Pyrazinamide (PZA) is a critical component of the first-line TB treatment regimen because of its sterilizing activity against non-replicating Mycobacterium tuberculosis (Mtb), but its mechanism of action has remained enigmatic. PZA is a prodrug converted by pyrazinamidase encoded by pncA within Mtb to the active moiety, pyrazinoic acid (POA) and PZA resistance is caused by loss-of-function mutations to pyrazinamidase. We have recently shown that POA induces targeted protein degradation of the enzyme PanD, a crucial component of the CoA biosynthetic pathway essential in Mtb. Based on the newly identified mechanism of action of POA, along with the crystal structure of PanD bound to POA, we designed several POA analogs using structure for interpretation to improve potency and overcome PZA resistance. We prepared and tested ring and carboxylic acid bioisosteres as well as 3, 5, 6 substitutions on the ring to study the structure activity relationships of the POA scaffold. All the analogs were evaluated for their whole cell antimycobacterial activity, and a few representative mols. were evaluated for their binding affinity, towards PanD, through isothermal titration calorimetry. We report that analogs with ring and carboxylic acid bioisosteres did not significantly enhance the antimicrobial activity, whereas the alkylamino-group substitutions at the 3 and 5 position of POA were found to be up to 5 to 10-fold more potent than POA. Further development and mechanistic anal. of these analogs may lead to a next generation POA analog for treating TB.

Keywords: Tuberculosis ; Pyrazinoic acid ; pyrazinamide

Alternative Products

Product Details of [ 5720-05-8 ]

CAS No. :5720-05-8
Formula : C7H9BO2
M.W : 135.96
SMILES Code : C1=C(B(O)O)C=CC(=C1)C
Synonyms :
p-Tolylboronic acid
MDL No. :MFCD00039138
InChI Key :BIWQNIMLAISTBV-UHFFFAOYSA-N
Pubchem ID :79799

Safety of [ 5720-05-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P403+P233-P405-P501

Computational Chemistry of [ 5720-05-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 2.0
Molar Refractivity 41.23
TPSA ?

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

40.46 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

1.19
Log Po/w (WLOGP)?

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

-0.33
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.

0.61
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

-0.3
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.24

Water Solubility

Log S (ESOL):?

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

-1.81
Solubility 2.1 mg/ml ; 0.0155 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.64
Solubility 3.15 mg/ml ; 0.0231 mol/l
Class?

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

Very 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

-1.64
Solubility 3.09 mg/ml ; 0.0227 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

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

Yes
Log Kp (skin permeation)?

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

-6.28 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

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)

1.32

Application In Synthesis of [ 5720-05-8 ]

* 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 [ 5720-05-8 ]

[ 5720-05-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 5720-05-8 ]
  • [ 1072-84-0 ]
  • 1-<i>p</i>-tolyl-1<i>H</i>-imidazole-4-carboxylic acid amide [ No CAS ]
  • 2
  • [ 5720-05-8 ]
  • [ 72716-80-4 ]
  • 5,6-dimethyl-1-(4-methylphenyl)-2-oxo-1,2-dihydropyridin-3-carbonitrile [ No CAS ]
  • 3
  • [ 5720-05-8 ]
  • [ 17114-97-5 ]
  • 3-<i>tert</i>-butoxy-2-<i>p</i>-tolylamino-propionic acid methyl ester [ No CAS ]
  • 4
  • [ 1920-66-7 ]
  • [ 5720-05-8 ]
  • 4-amino-5-nitro-2-(4-methylphenyl)pyrimidine [ No CAS ]
  • 5
  • [ 5720-05-8 ]
  • [ 459-57-4 ]
  • [ 345-91-5 ]
  • [ 530-46-1 ]
  • 7
  • [ 5720-05-8 ]
  • [ 309947-86-2 ]
  • di(tert-butyl) 9-p-tolyl-9H-purin-6-yliminodicarbonate [ No CAS ]
  • 8
  • [ 5720-05-8 ]
  • [ 4016-63-1 ]
  • [ 79953-04-1 ]
  • 9
  • [ 5720-05-8 ]
  • [ 30913-86-1 ]
  • [ 497-19-8 ]
  • 4-(4'-Methyl-biphenyl-4-yl)-4-oxo-butyric acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
tetrakis(triphenylphosphine)palladium (0); In chloroform; toluene; Step (b) Preparation of 4-(4'-Methyl-biphenyl-4-yl)-4-oxo-butyric acid methyl ester To a stirred mixture of (4-methylphenyl)boronic acid (0.818 g, 0.00602 mol) and 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (1.3556 g, 0.00500 mol) in toluene (10 mL) was added tetrakis(triphenylphosphine)-palladium(0) (0.173 g, 0.000150 mol) and 2.0 M aqueous sodium carbonate (5.0 mL, 0.010 mol), and the mixture was heated at reflux under nitrogen for 12 hours and allowed to cool. The mixture was diluted with toluene and dichloromethane (10 mL/10 mL), and filtered through a pad of Celite. The Celite was washed with additional toluene and dichloromethane. Filtrate and washings were combined and washed with 2.0 M aqueous sodium carbonate, brine, 3% aqueous ammonium hydroxide, water, and brine. The organics were dried (Na2SO4) and rotary evaporated. The residue was dissolved in chloroform and purified by column chromatography on silica gel (144 g, 230-400 mesh), eluding with hexanes-acetone (6:1, 17*125 mL) to give 0.98 g of 4-(4'-methyl-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 121-122 C.
  • 10
  • [ 5720-05-8 ]
  • [ 1194-22-5 ]
  • 2-methyl-4,6-bis(4-tolyl)pyrimidine [ No CAS ]
  • 11
  • [ 1003-91-4 ]
  • [ 5720-05-8 ]
  • [ 1246624-41-8 ]
  • 12
  • [ 19063-55-9 ]
  • [ 5720-05-8 ]
  • [ 1259294-15-9 ]
  • 13
  • [ 56734-10-2 ]
  • [ 5720-05-8 ]
  • [ 77232-22-5 ]
  • 14
  • [ 1403257-80-6 ]
  • [ 5720-05-8 ]
  • [ 1403255-82-2 ]
YieldReaction ConditionsOperation in experiment
73% With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 100℃; for 2h;Inert atmosphere; Example 112 Synthesis of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4,4'-dimethyl-[1,1'-biphenyl]-3-carboxamide To a stirred solution <strong>[1403257-80-6]5-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-2-methylbenzamide</strong> (200 mg, 0.42 mmol) and p-tolyl boronic acid (86 mg, 0.63 mmol) in dioxane (3 mL), aqueous 2M Na2CO3 solution (0.75 mL, 1.51 mmol) was added and solution was purged with argon for 15 min. Then Pd(PPh3)4 (48 mg, 0.04 mmol) was added and argon was purged again for 15 min. Reaction mass was heated at 100 C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by column chromatographic purification afforded the title compound (150 mg, 73%). LCMS: 488.20 (M+1)+; HPLC: 99.33% ( 254 nm) (Rt; 5.393; Method: Column: YMC ODS-A 150 mm*4.6 mm*5mu; Mobile Phase: A; 0.05% TFA in water/B; 0.05% TFA in acetonitrile; Inj. Vol: 10 muL, Col. Temp.: 30 C.; Flow rate: 1.4 mL/min.; Gradient: 5% B to 95% B in 8 min, Hold for 1.5 min, 9.51-12 min 5% B); 1H NMR (DMSO-d6, 400 MHz) delta 11.46 (s, 1H), 8.19 (t, 1H), 7.51 (d, 2H, J=8 Hz), 7.37 (s, 1H), 7.25 (d, 2H, J=8 Hz), 7.19 (s, 1H), 5.85 (s, 1H), 4.28 (d, 2H, J=4.4 Hz), 3.81-3.83 (m, 2H), 3.22-3.27 (m, 2H), 3.07-3.09 (m, 2H), 3.01 (m, 1H), 2.33 (s, 3H), 2.23 (s, 3H), 2.20 (s, 3H), 2.10 (s, 3H), 1.64-1.67 (m, 2H), 1.51-1.55 (m, 2H), 0.82 (t, 3H, J=6.8 Hz).
  • 15
  • [ 80041-89-0 ]
  • [ 5720-05-8 ]
  • [ 618-39-3 ]
  • [ 1410809-28-7 ]
  • 16
  • [ 5720-05-8 ]
  • [ 34259-99-9 ]
  • [ 1826-19-3 ]
  • 17
  • [ 4265-25-2 ]
  • [ 5720-05-8 ]
  • [ 64-19-7 ]
  • 2-methyl-(p-tolyl)-2,3-dihydrobenzofuran-3-yl acetate [ No CAS ]
  • 2-methyl-(p-tolyl)-2,3-dihydrobenzofuran-3-yl acetate [ No CAS ]
  • 18
  • [ 5720-05-8 ]
  • [ 25569-77-1 ]
  • [ 530-46-1 ]
  • 19
  • [ 129488-10-4 ]
  • [ 5720-05-8 ]
  • 5-[(4-methylphenyl)amino]-1H-indazole-1-carboxylic acid tert-butyl ester [ No CAS ]
  • 20
  • [ 5720-05-8 ]
  • [ 380430-55-7 ]
  • 21
  • [ 5720-05-8 ]
  • [ 530-46-1 ]
  • 22
  • [ 1120-95-2 ]
  • [ 5720-05-8 ]
  • [ 52432-27-6 ]
  • 23
  • [ 13304-62-6 ]
  • [ 5720-05-8 ]
  • C17H18FNO [ No CAS ]
  • 24
  • [ 88-12-0 ]
  • [ 383-62-0 ]
  • [ 5720-05-8 ]
  • ethyl 2,2-difluoro-4-(N-methylacetamido)-4-(p-tolyl)butanoate [ No CAS ]
  • 25
  • [ 88-12-0 ]
  • [ 383-62-0 ]
  • [ 5720-05-8 ]
  • ethyl 2, 2-difluoro-4-(2-oxopyrrolidin-1-yl)-4-(p-tolyl)butanoate [ No CAS ]
  • 26
  • [ 3485-84-5 ]
  • [ 383-62-0 ]
  • [ 5720-05-8 ]
  • 3, 3-difluoro-5-(p-tolyl)pyrrolidin-2-one [ No CAS ]
  • 27
  • [ 5720-05-8 ]
  • [ 403-43-0 ]
  • [ 530-46-1 ]
YieldReaction ConditionsOperation in experiment
94% With sodium hydroxide; In toluene; at 100℃; for 2h;Schlenk technique; General procedure: An oven-dried Schlenk flask, equipped with a magnetic stir bar, septum and a condenser was charged with acyl chloride (1.0 mmol), arylboronic acid (1.0 mmol), NaOH (4 mmol) and 5.0 mL of toluene. The flask was immersed and stirred in an oil bath at 100 °C. Upon complete consumption of starting materials as determined by GC analysis, the water (10.0 mL) was added. The reaction mixture was extracted with diethyl ether (3 × 5.0 mL). The combined organic layer was collected, dried over anhydrous Na2SO4 and concentrated in vacuum to afford product which was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 9:1 or 8:2).
  • 28
  • [ 456-22-4 ]
  • [ 5720-05-8 ]
  • [ 530-46-1 ]
YieldReaction ConditionsOperation in experiment
54% With di-tert-butyl dicarbonate; potassium carbonate; magnesium chloride; nickel dichloride; zinc; In tetrahydrofuran; at 20℃; for 20h; Weigh 1mmol of p-fluorobenzoic acid and 0.5mmol of p-methylbenzeneboronic acid in the reaction flask, With tetrahydrofuran as solvent, 6.5 mg of nickel chloride (0.05 mmol) 98 mg zinc powder (1.5 mmol), 8 mg of bipyridine (0.05 mmol), 138 mg of potassium carbonate (1.0 mmol), 143 mg of magnesium chloride (1.5 mmol), 109 mg of di-tert-butyl dicarbonate (0.5 mmol), The reaction was stirred at room temperature for 20h, to give the desired product isolated 58mg, yield 54percent
  • 29
  • [ 877399-50-3 ]
  • [ 5720-05-8 ]
  • 4-[4-(p-tolyl)pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
139 mg With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In water; N,N-dimethyl-formamide; at 80℃; To <strong>[877399-50-3]4-(4-bromopyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester</strong> (208 mg) were added 4-methylphenylboronic acid (95 mg),N,N-dimethylformamide (3.2 mL),2 M aqueous sodium carbonate solution (946 muL) and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II)dichloride. dichloromethane complex (26 mg) and the mixture was stirred at 80°c. After completion of the reaction,saturated brine was added and the mixture was extracted with ethyl acetate. The solvent was evaporated and the obtained residue was purified by column chromatography (hexane:ethyl acetate)to give 4-[4-(p-tolyl)pyrazol-1-yl]piperidine-1-carboxylic acid tert-butyl ester (139 mg).
  • 31
  • [ 886371-28-4 ]
  • [ 5720-05-8 ]
  • 6-chloro-3-(p-tolyl)imidazo[1,2-a]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 50.0℃; for 5.0h;Inert atmosphere; General procedure: To an oven dried 5 mL microwave vessel was addedPd(dppf)Cl2·CH2Cl2 (4 mol%), halide/pseudohalide (1 equiv),boron coupling partner (1 equiv), and Cs2CO3 (3 equiv). Thevessel was then capped and purged with N2 before addition ofCyrene (1 mL, 0.25 M) and H2O (1.8 mL). The reaction mixturewas heated to 50 C and maintained at this temperature withstirring for 5 h before the vessel was vented and decapped. Thesolution was then diluted with Et2O (10 mL) and washed withwater (2 × 20 mL) and brine (2 × 20 mL). The organics were thenpassed through a hydrophobic frit and concentrated underreduced pressure to give a residue, which was purified by flashchromatography (silica gel) to afford the title compound.
  • 32
  • [ 5720-05-8 ]
  • [ 21193-80-6 ]
  • 4-amino-5-(4-methylphenyl)-N7-(β-D-ribofuranosyl)-pyrrolo[2,3-d]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With trisodium tris(3-sulfophenyl)phosphine; palladium diacetate; sodium carbonate; In water; acetonitrile; at 100℃;Inert atmosphere; General procedure: 31 (1 eq.), boronic acid (1.5 eq.) or pinacol ester [for compound14 (1.5 eq.)], Na2CO3 (9 eq.), Pd(OAc)2 (0.05 eq.) and TPPTS (0.15 eq.)were added to a 10mL round-bottom flask, equipped with a stir bar.Next, the flask was evacuated and refilled with argon. This procedure was repeated three times in total. Next, degassed MeCN(2 mL/mmol SM) and H2O (4 mL/mmol SM) were added to the solids under argon. After 5 min of stirring, the mixture was heatedto 100 C in a pre-heated oil bath. When the starting material was fully consumed (usually 1e3 h), the mixture was cooled to ambient temperature, and neutralized (pH ~ 7) with 0.5M aq. HCl. Themixture was evaporated till dryness, resuspended in MeOH and evaporated (three times). Next, the mixture was adsorbed onto Celite (fromMeOH) and eluted over a short silica pad (~5 cm) with 20% MeOH/DCM. The liquid was evaporated in vacuo and purified by column chromatography.
  • 33
  • [ 5720-05-8 ]
  • [ 5350-41-4 ]
  • [ 620-83-7 ]
  • 34
  • [ 19935-81-0 ]
  • [ 5720-05-8 ]
  • 1-methyl-4-(1-(4-nitrophenyl)ethyl)benzene [ No CAS ]
  • 35
  • [ 352-34-1 ]
  • [ 5720-05-8 ]
  • [ 13939-06-5 ]
  • [ 530-46-1 ]
 

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