Welcome to LookChem.com Sign In|Join Free

CAS

  • or

169590-42-5

Post Buying Request

169590-42-5 Suppliers

Recommended suppliersmore

  • Product
  • FOB Price
  • Min.Order
  • Supply Ability
  • Supplier
  • Contact Supplier

169590-42-5 Usage

Indications and Usage

Celecoxib and Rofecoxib are two currently used COX-2 inhibitors. Successfully developed by GD Searle & Pfizer Co. (U.S.,) released in 1999, trade name: Celebrex. Celecoxib is a nonsteroidal, anti-inflammatory agent with significant analgesic and anti-inflammatory effects, causing the lowest incidence of upper gastrointestinal tract ulcers and other complications. Used clinically to treat acute and chronic osteoarthritis and rheumatoid arthritis, with an anti-inflammatory analgesic role, relieving the signs and symptoms of osteoarthritis and rheumatoid arthritis.

Application in Particular Diseases

In Osteoarthritis: As a Cyclooxygenase-2 (COX-2) selective inhibitor, Celecoxib demonstrate analgesic benefits that are similar to traditional nonselective NSAIDs. Although COX-2 selective inhibition was designed to reduce NSAIDinduced gastropathy (e.g., ulcers, bleeding, perforation), concerns about adverse cardiovascular events (e.g., myocardial infarction, stroke) have led authorities to recommend their use only in selected patients who are at high risk for NSAID-related GI effects and low risk for cardiovascular toxicity.

Mechanisms of Action

Celecoxib has the anti-inflammatory and analgesic effect of NSAIDs. Because of its chemical structure, it can be combined with COX-2, selectively inhibiting COX-2. Its phenyl group binds with the hydrophobic channel of COX-2, and its hydrophilic sulfonamide forms a hydrogen chain with 513 arginine and 90 histidine in the COX-2 "side pocket.” It is also in close contact with arginine in the COX-2120 position and plays a role in inhibiting COX-2 from converting arachidonic acid to prostaglandins which are harmful to the human body. Due to subtle differences between the structures of COX-1 and COX-2, Celecoxib cannot enter the COX-1 molecule, nor inhibit its transformation of arachidonic acid into prostaglandins.? Thus, it has good anti-inflammatory and analgesic effects, protects gastric mucosa, protects renal blood flow, regulates platelet aggregation, and resolves the gastric irritation problems of commonly used NSAIDs.

Pharmacokinetics

Different sources of media describe the Pharmacokinetics of 169590-42-5 differently. You can refer to the following data:
1. Celecoxib can be quickly absorbed after oral administration, with peak concentration at about 3h. The peak concentration of a single oral dose of 200 mg is 705 ng/ml. After absorption, up to 97% binds to plasma proteins; the drug is widely distributed, with apparent volume of distribution (455±166)L. Metabolized in vivo through P450(CYP)2C9 liver enzyme metabolism. Combined with carboxylic acid and glucuronide through biotransformation, about 2% of original amount excreted in urine and feces. Half-life about 1h. Drug disposition and pharmacokinetics vary with race and age, amplifying total mild liver absorption damage (AUC.) When ingested with high fat peak plasma concentration effects are extended 1-2h, and AUC increases 10%-20%. When taken with aluminum and magnesium antacids peak concentration is reduced 37%, and AUC decreases 10%. No interaction with warfarin, ketoconazole, or methotrexate (MTX.) Clinically significant interactions with fluconazole and lithium, reducing Cmax 37% and AUC 10%。
2. Celecoxib is well absorbed from the GI tract, with peak plasma concentrations generally being attained within 3 hours of administration. Peak plasma levels in geriatric patients may be increased, but dosage adjustments in elderly patients generally are not required unless the patient weighs less than 50 kg.

Clinical Research

50 Clinical trials on more than 130,000 subjects in 23 countries have been conducted on Celecoxib. Regarding anti-inflammatory and analgesic effects towards osteoarthritis (OA) and rheumatoid arthritis (RA): subjects ages 18-93 had been diagnosed with OA or RA for at least three months, and the disease was in an active or relapsed state. Diagnoses were made according to the criteria of the American College of Rheumatology (ACR.) Visual analog scales (VAS) and American Pain Society (APS) test tables were used to evaluate joint pain, and the WOMAC and health assessment questionnaire (HAQ) impaired function indices were used to evaluate joint pain, stiffness, and function loss. Extensive clinical trials have shown that Celecoxib is effective against OA and RA joint pain. Clinical trials on the efficacy of Celecoxib against OA have concluded: by VAS evaluation, 100 and 200 mg bid have the same effect on reducing signs and symptoms of OA as with 500 mg bid of naproxen, greater than with placebos, although the effects of 200 mg bid are not significantly greater than those with 100 mg bid. The effects on OA pain last 24-48h, equivalent to 500 mg bid of naproxen. Using the WOMAC (pain, joint stiffness, and impaired function) indices, 100 and 200 mg bid had the same effects as 500 mg bid of naproxen. 200 mg qd and 100 mg bid had similar effects on OA symptoms. For RA: 100 and 200 mg bid significantly relieved RA symptoms in clinical trials, equivalent to 500 mg bid of naproxen. 100, 200, and 400 mg bid had similar effects on the number of RA patients suffering from joint swelling and pain/tenderness, all equivalent to 500 mg bid of naproxen.

Side Effects

Occasional gastrointestinal reactions. Small effects on renal function and platelets. Acute overdose can cause fatigue, drowsiness, nausea, vomiting, and upper abdominal pain, which can be relieved with treatment. Gastrointestinal bleeding is possible. In rare cases, hypertension, acute renal failure, respiratory depression, and comas may occur.

Warnings and Precautions

Anyone who is allergic to any ingredient in Celecoxib or who is known to be allergic to sulfa drugs should not take it. It should be avoided in patients with asthma, urticaria, or acute rhinitis. Lactating women should not take it. May slow down metabolism and increase serum concentration in combination with leukotriene antagonist zafirlukast, antifungal agent fluconazole, and lipid-lowering statin drug fluvastatin. Celecoxib can increase blood concentration of beta blockers, antidepressants and antipsychotic drugs, so care should be taken when using these drugs.

Description

Celecoxib is a nonsteroidal antiinflammatory drug (NSAID) first launched as Celebrex in the US for the treatment of symptoms in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Celecoxib belongs to a new class of 1, 5-diarylpyrazoles and can be synthesized by heat-promoted heterocyclization of a trifiuoro-l,3-dione with appropriate arylhydrazine. Celecoxib is a highly selective inhibitor of COX-2, the inducible form of cyclooxygenase expressed during inflammatory processes; it does not block the constitutive form COX-1, thus suppressing the gastric and intestinal toxicity of most non-selective NSAIDs. The potency ratio COX1/COX2 on purified human enzymes was about 400. In several in vivo models of acute and chronic inflammation, Celecoxib demonstrated potent antiinflammatory activity without affecting gastric or urinary prostaglandin PGE2. In several clinical studies performed with patients suffering from osteoarthritis or rheumatoid arthritis, Celecoxib was shown to be well tolerated and to relieve pain and inflammation more efficiently compared with other standard NSAIDs; the gastrointestinal safety profile was significantly better than that of other NSAIDs. Interestingly, Celecoxib was approved for another indication in patients with familial adenomatous polyposis (FAP). A six-month clinical trial demonstrated a 28% reduction in the number of colorectal polyps with Celecoxib, compared to a 5% reduction with placebo.

Chemical Properties

White to Pale Yellow Solid

Originator

Searle (US)

Uses

Different sources of media describe the Uses of 169590-42-5 differently. You can refer to the following data:
1. expectorant, gastric stimulant, insecticide
2. For relief and management of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), ankylosing spondylitis, acute pain, primary dysmenorrhea and oral adjunct to usual care for patients with familial adenomatous polyposis
3. A selective cyclooxygenase-2 (COX-2) inhibitor. Anti-inflammatory. Used in treatment of familial adenomatous polyposis

Indications

Celecoxib is indicated for the treatment of osteoarthritis and rheumatoid arthritis. Its use is contraindicated in individuals with hypersensitivity to sulfonamides or other NSAIDs. It should be used with caution in persons with hepatic disease. Interactions occur with other drugs that induce CYP2C9 (e.g. rifampin rifampin) or compete for metabolism by this enzyme (e.g. fluconazole, leflunomide). The most common adverse reactions to celecoxib are mild to moderate GI effects such as dyspepsia, diarrhea, and abdominal pain. Serious GI and renal effects have occurred rarely.

Manufacturing Process

4-(5-(4-Methylphenyl)-3-trifluoromethyl-N-pyrazol-1-yl)benzenesulfonamide To a solution of ethyl trifluoroacetate (1.90 ml, 16.0 mmol) in 7 ml of methyl tert-butyl ether was added 25% NaOMe (3.62 ml, 16.8 mmol). Next 4- chloroaceteophenone (2.08 ml, 16.0 mmol) in 2 ml of methyl tert-butyl ether was added. The mixture was stirred at room temperature overnight. To above solution was added 100 ml of 90% EtOH, followed by 4 N HCl (4.0 ml, 16 mmol) and 4-sulphonamidophenylhydrazine hydrochloride (3.58 g, 16 mmol). The mixture was heated to reflux for 3 hours. The mixture was concentrated. When 30 ml of water was added, a solid formed. The solid was filtered and washed with 20 ml of 60% EtOH to give 4.50 g of white solid. The filtrate was evaporated and taken up in ethyl acetate (100 ml), washed with saturated NaHCO3, and brine, dried over MgSO4, and concentrated. Heptane was added at boiling point of the mixture. After cooling down to 0°C, 1.01 g more product was obtained. The combined yield of the 4-(5-(4-methylphenyl)-3- trifluoromethyl-N-pyrazol-1-yl)benzenesulfonamide (Celecoxib) was 86%.

Brand name

Celebrex (Searle).

Therapeutic Function

Antiinflammatory

General Description

Celecoxib (Celebrex) was the first selective COX-2 inhibitordrug introduced into the market in 1998 for use in thetreatment of RA, OA, acute pain, and menstrual pain. Thereal benefit is that it has caused fewer GI complicationswhen compared with other conventional NSAIDs. It hasalso been approved for reducing the number of adenomatouscolorectal polyps in familial adenomatous polyposis (FAP).Celecoxib is well absorbed and undergoes rapid oxidativemetabolism via CYP2C9 to give its inactive metabolites. Thus, a potential drug interaction exists betweencelecoxib and warfarin because the active isomer ofwarfarin is primarily degraded by CYP2C9.

Biological Activity

Selective cyclooxygenase-2 (COX-2) inhibitor (IC 50 values are 15 and 0.04 μ M for COX-1 and COX-2 respectively). Anti-inflammatory with shorter plasma half-life in vivo than SC 58121 (5-(4-Fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole ). Displays chemopreventive activity in in vivo tumor models.

Biochem/physiol Actions

Celecoxib is a non-steroidal, anti-inflammatory drug (NSAID) and a cyclooxygenase-2 (COX-2) selective inhibitor. Celecoxib is at least 10-20 times more selective for COX-2 over COX-1.

Clinical Use

Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib is synthesized by condensing 4-methyl-acetophenone and ethyltrifluoroacetate with sodium methoxide and the resulting butanedione derivative cyclized with 4-hydrazinophenylsulfonamide. It was the first NSAID to be marketed as a selective COX-2 inhibitor.

in vitro

celecoxib not only reduced the production of pge2 but also inhibited the downstream effects of pge2. celecoxib blocked migration and invasion of a549 cells increased by pge2 in the wound healing and transwell assays. additionally, celecoxib reduced mmp9 mrna expression which was increased by pge2. moreover, celecoxib enhanced e-cadherin mrna expression which was inhibited by pge2 [2].

in vivo

celecoxib inhibited the increase in metastases of a549 cells and significantly reduced the increase in pge2 plasma level in mice receiving unilateral pneumonectomy [2].

Drug interactions

Potentially hazardous interactions with other drugsACE inhibitors and angiotensin-II antagonists: antagonism of hypotensive effect; increased risk of nephrotoxicity and hyperkalaemia.Analgesics: avoid concomitant use of 2 or more NSAIDs, including aspirin (increased side effects); avoid with ketorolac (increased risk of side effects and haemorrhage).Antibacterials: possibly increased risk of convulsions with quinolones; concentration reduced by rifampicinAnticoagulants: effects of coumarins and phenindione enhanced; possibly increased risk of bleeding with heparins, dabigatran and edoxaban - avoid long term use with edoxaban.Antidepressants: increased risk of bleeding with SSRIs and venlaflaxine.Antidiabetic agents: effects of sulphonylureas enhancedAntiepileptics: possibly increased phenytoin concentration.Antifungals: if used with fluconazole, halve the dose of celecoxib.Antivirals: increased risk of haematological toxicity with zidovudine; concentration possibly increased by ritonavir.Ciclosporin: may potentiate nephrotoxicityCytotoxics: reduced excretion of methotrexate; increased risk of bleeding with erlotinib.Diuretics: increased risk of nephrotoxicity; antagonism of diuretic effect; hyperkalaemia with potassium-sparing diuretics.Lithium: excretion decreased.Pentoxifylline: possibly increased risk of bleedingTacrolimus: increased risk of nephrotoxicity.

Metabolism

Celecoxib is excreted in the urine and feces primarily as inactive metabolites, with less than 3% of an administered dose being excreted as unchanged drug. Metabolism occurs primarily in the liver by CYP2C9 and involves hydroxylation of the 4-methyl group to the primary alcohol, which is subsequently oxidized to its corresponding carboxylic acid, the major metabolite (73% of the administered dose). The carboxylic acid is conjugated, to a slight extent, with glucuronic acid to form the corresponding glucuronide. None of the isolated metabolites have been shown to exhibit pharmacological activity as inhibitors of either COX-1 or COX-2. Celecoxib also inhibits CYP2D6; thus, the potential of celecoxib to alter the pharmacokinetic profiles of other drugs inhibited by this isoenzyme exists. Celecoxib, however, does not appear to inhibit other CYP isoforms, such as CYP2C19 or CYP3A4. Other drug interactions related to the metabolic profile of celecoxib have been noted, particularly with other drugs that inhibit CYP2C.

References

1) Penning . (1997), Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-58635, celecoxib); J. Med. Chem., 40 1347 2) DeWitt et al. (1999), Cox-2-selective inhibitors: the new super aspirins; Mol. Pharmacol., 55 625 3) Harris et al. (2000), Chemoprevention of breast cancer in rats by celecoxib, a cyclooxygenase 2 inhibitor; Cancer Res., 60 2101 4) Koki and Masferrer et al. (2002), Celecoxib: a specific COX-2 inhibitor with anticancer properties; Cancer Control, 9 28

Check Digit Verification of cas no

The CAS Registry Mumber 169590-42-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,9,5,9 and 0 respectively; the second part has 2 digits, 4 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 169590-42:
(8*1)+(7*6)+(6*9)+(5*5)+(4*9)+(3*0)+(2*4)+(1*2)=175
175 % 10 = 5
So 169590-42-5 is a valid CAS Registry Number.
InChI:InChI=1/C17H14F3N3O2S/c1-11-2-4-12(5-3-11)15-10-16(17(18,19)20)22-23(15)13-6-8-14(9-7-13)26(21,24)25/h2-10H,1H3,(H2,21,24,25)

169590-42-5 Well-known Company Product Price

  • Brand
  • (Code)Product description
  • CAS number
  • Packaging
  • Price
  • Detail
  • Sigma-Aldrich

  • (Y0001445)  Celecoxib  European Pharmacopoeia (EP) Reference Standard

  • 169590-42-5

  • Y0001445

  • 1,880.19CNY

  • Detail
  • USP

  • (1098504)  Celecoxib  United States Pharmacopeia (USP) Reference Standard

  • 169590-42-5

  • 1098504-200MG

  • 4,326.66CNY

  • Detail

169590-42-5SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 18, 2017

Revision Date: Aug 18, 2017

1.Identification

1.1 GHS Product identifier

Product name celecoxib

1.2 Other means of identification

Product number -
Other names N-[4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1yl]phenylsulfonyl]benzensulfonamide

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:169590-42-5 SDS

169590-42-5Synthetic route

4,4,4-trifluoro-1-(4-methylphenyl)butane-1,3-dione
720-94-5

4,4,4-trifluoro-1-(4-methylphenyl)butane-1,3-dione

4-hydrazinobenzene-1-sulfonamide hydrochloride
17852-52-7, 27918-19-0

4-hydrazinobenzene-1-sulfonamide hydrochloride

4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide
169590-42-5

4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide

Conditions
ConditionsYield
at 90℃; Temperature;99%
In ethanol Reflux;90%
In methanol; water at 120℃; under 24002.4 Torr; for 0.221667h; Temperature; Pressure; Time; Solvent; Flow reactor;85%
N,N-dibenzyl-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
853793-24-5

N,N-dibenzyl-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide

4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide
169590-42-5

4-[5-(4-(methyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulphonamide

Conditions
ConditionsYield
With sulfuric acid at 20℃; for 8h;99%
With sulfuric acid at 20℃; for 4h;70%
With sulfuric acid at 20℃; for 2h;69%

169590-42-5Downstream Products

169590-42-5Relevant articles and documents

Bioorthogonal release of sulfonamides and mutually orthogonal liberation of two drugs

Shao, Zhuzhou,Liu, Wei,Tao, Huimin,Liu, Fang,Zeng, Ruxin,Champagne, Pier Alexandre,Cao, Yang,Houk,Liang, Yong

, p. 14089 - 14092 (2018)

Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.

Synthesis of [11C]celecoxib: A potential PET probe for imaging COX-2 expression

Prabhakaran, Jaya,Majo, Vattoly J.,Simpson, Norman R.,Van Heertum, Ronald L.,Mann, J. John,Kumar, J. S. Dileep

, p. 887 - 895 (2005)

[11C]Labeling of celecoxib, a COX-2 selective inhibitor and prescription drug for arthritis and pain has been achieved. The precursor molecule for the radiolabeling was synthesized from 4-bromoacetophenone in 4 steps with 23% overall yield. Stille reaction of N-[bis-(4-methoxyphenyl) phenylmethyi]-4-[5-(4-tributylstannylphenyl)-3-trifluoromethylpyrazol-1-yl] benzenesulfonamide (5) with methyl iodide in presence of catalytic amounts of Pd2(dba)3, tri-o-tolylphosphine, CuCl and excess of K 2CO3 in DMF followed by deprotection of the sulfonamide with 20% trifluoroaceticacid yielded 4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl) benzenesulfonamide or celecoxib (6) in 30% yield. However, under identical conditions, synthesis of [11C]celecoxib ([11C]6) was unsuccessful. Instead, trapping [11C]CH3I in an argon purged solution of catalytic amounts of Pd2(dba)3 and tri-o-tolylphosphine followed by the addition of the precursor 5 in DMF under argon and heating the mixture at 135°C for 4 min resulted in the incorporation of [11C]CH3 group. Removal of the dimethoxytrityl (DMT) with 20% trifluoroacetic acid afforded [ 11C]celecoxib in 40 min (EOB) and 8 ± 2% yield (EOB) along with a specific activity of 1080 ± 180 Ci/mmol (n = 6) (EOB). Copyright

Design and synthesis of novel celecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: Replacement of the sulfonamide pharmacophore by a sulfonylazide bioisostere

Uddin, Md. Jashim,Rao, P.N. Praveen,Knaus, Edward E.

, p. 5273 - 5280 (2003)

A group of celecoxib analogues in which the para-SO2NH 2 substituent on the N1-phenyl ring was replaced by a para-sulfonylazido (SO2N3) 4, or a meta-SO 2N3 8, substituent were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that 4-[5-(4-methylphenyl)-3-trifluoromethyl-1H- pyrazol-1-yl]benzenesulfonyl azide (4) with a para-SO2N3 substituent was a selective COX-1 inhibitor. In contrast, 3-[5-(4-methylphenyl)- 3-trifluoromethylpyrazol-1-yl]benzenesulfonyl azide (8a) having a meta-SO 2N3 substituent (COX-1 IC50 >100 μM; COX-2 IC50=5.16 μM; COX-2 selectivity index >19.3) is a selective COX-2 inhibitor. A molecular modeling (docking) study showed that the SO2N3 group of 8a inserts deep inside the secondary pocket of the COX-2 binding site. The SO2N3 moiety of 8a can undergo a dual H-bonding interaction via one of its SO2 oxygen-atoms, and an electrostatic (ion-ion) interaction via the terminal azido (N3) nitrogen-atom, to the guanidino NH2 of Arg 513 in the secondary pocket of COX-2. These observations indicate that an appropriately positioned SO2N3 moiety is a novel alternative bioisostere to the traditional SO2NH2 and SO2Me pharmacophores present in selective COX-2 inhibitors, that are only capable of H-bonding interactions with the COX-2 isozyme, for use in drug design.

Application of (MWCNTs)-COOH/CeO2 hybrid as an efficient catalyst for the synthesis of some nitrogen-containing organic compounds

Heidarzadeh, Tahereh,Nami, Navabeh,Zareyee, Daryoush

, (2021/08/18)

ABSTRACT: Modification of acid functionalized multi-walled carbon nanotubes (MWCNTs)-COOH with CeO2 nanoparticles using Ce(NO3)2.6H2O, produced an efficient catalyst for the synthesis of some nitrogen-containing heterocycles such as celecoxib. The products were identified by CHN analysis, NMR, and FT-IR spectra. On the other hand, synthesis of CeO2 nanoparticles and their conjugation on the surface of (MWCNTs)-COOH have been confirmed by FT-IR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Energy-dispersive X-ray spectroscopy (EDX).

Rapid Access to N-Protected Sulfonimidoyl Fluorides: Divergent Synthesis of Sulfonamides and Sulfonimidamides

Liu, Yongan,Pan, Qijun,Hu, Xiaojun,Guo, Yong,Chen, Qing-Yun,Liu, Chao

, p. 3975 - 3980 (2021/05/26)

Herein we report a practical and efficient copper-catalyzed approach for the conversion of various arenediazonium salts to the corresponding N-protected sulfonimidoyl fluorides. This operationally simple protocol tolerates a wide range of functional groups and can be applied to the late-stage modification of complex bioactive molecules. Furthermore, pharmaceutically important primary sulfonamides and sulfonimidamides derived from these valuable N-protected sulfonimidoyl fluoride units were prepared in minimal synthetic steps.

HFO-1234yf as a CF3-Building Block: Synthesis and Chemistry of CF3-Ynones

Murray, Ben J.,Marsh, Thomas G. F.,Yufit, Dmitri S.,Fox, Mark A.,Harsanyi, Antal,Boulton, Lee T.,Sandford, Graham

, p. 6236 - 6244 (2020/09/15)

Reaction of low cost, readily available 4th generation refrigerant gas 2,3,3,3-tetrafluoropropene (HFO-1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3-trifluoropropynide, addition of which to a range of aldehydes formed CF3-alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess–Martin periodinane (DMP) to give substituted CF3-ynones with minimal purification required. Michael-type additions of alcohol and amine nucleophiles to CF3-ynones are rapid and selective, affording a range of CF3-enone ethers and enaminones in excellent yields with high stereoselectivity for the Z-isomer. By analogous reactions with difunctional nucleophiles, a wide range of CF3-substituted pharmaceutically relevant heterocyclic structures can be accessed, exemplified in the simple synthesis of the anti-arthritis drug celecoxib from HFO-1234yf in just three steps.

Post a RFQ

Enter 15 to 2000 letters.Word count: 0 letters

Attach files(File Format: Jpeg, Jpg, Gif, Png, PDF, PPT, Zip, Rar,Word or Excel Maximum File Size: 3MB)

1

What can I do for you?
Get Best Price

Get Best Price for 169590-42-5