134523-00-5 Usage
Chemical Properties
white Crystalline powder
Originator
Cardyl,Pfizer,Spain
Uses
antihyperlipoproteimic;HMG-CoA reductase inhibition
Manufacturing Process
285 ml 2.2 M n-butyl lithium in hexane was added dropwise to 92 ml
diisopropylamine at -50-60°C under nitrogen. The well stirred solutions
warmed to about -20°C, then it was cannulated into a suspension of 99 g of
S(+)-2-acetoxy-1,1,2-triphenylethanol in 500 ml absolute tetrahydrophuran
(THF) at -70°C and the reaction mixture was allowed to warm to -10°C for 2
hours. A suspension of MgBr2 was made from 564 ml (0.63 mol) of bromine
and 15.3 g of magnesium (0.63 mol) in 500 ml THF cooled to -78°C. The
enolate solution was cannulated into this suspension within 30 min and was
stirred for 60 min at -78°C. 150 g 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(3-
oxopropyl)-N,4-diphenyl-1H-pyrrole-3-carboxamide in 800 ml absolute THF
was added dropwise over 30 min, stirred 90 min at -78°C, then was added
200 ml acetic acid, this is removed to a cool bath, 500 ml of H2O was added
and the mixture concentrate in vacuo at 40-50°C. After adding of 500 ml of
1:1 EtOAc/heptane the mixture was filtered. The filtrate was washed
extensively with 0.5 N HCl, then several times with H2O and finally EtOAc/heptane (3:1) and cooled with dry ice to -20°C. The light brown
crystalline product was dried in vacuum oven at 40°C. The yield was 194 g.
112 g of the same product was produced by evaporation of mother liquor
after recrystallization and chromatographic purification on a silicagel.
162 g of this substance was suspended in methanol/THF (5:3) and was stirred
with 11.7 g of sodium methoxide until everything was dissolved and kept in
the freezer overnight. Later it was quenched with AcOH concentrated in vacuo,
was added to 500 ml H2O and extracted twice with EtOAc (300 ml). The
combined extracts was washed with saturated NaHCO3 brine and dried over
anhydrous MgSO4, purified on silica-gel and gave 86.1 g of white crystals m.p.
125-126°C, αD
20=4.23° (1.17 M, CH3OH).
81 g of the last product in 500 ml absolute THF was added as quickly as
possible to the mixture of 77 ml THF at diisopropylamine, 200 ml 2.2 M of nbutyl
lithium and 62 ml of t-butylacetate in 200 ml THF -40-42°C under
nitrogen. Stirring was continued for 4 hours at -70°C. The reaction mixture
was concentrated in vacuo, the residue was taken up in EtOAc, washed with
water, then saturated NH4Cl, NaHCO3 (saturated), dried over anhydrous
MgSO4, filtred and the solvent evaporated.
The organic phase was dried and concentrated in vacuo to yield 73 g crude
product, that was dissolved in 500 ml absolute THF, 120 ml triehtylborane and
0.7 g t-butylcarboxylic acid, 70 ml methanol and 4.5 g sodium borohydride
was added. The mixture was stirred at -78°C under a dry atmosphere for 6
hours, poured slowly into 4:1:1 mixture of ice/30%H2O2/H2O and stirred
overnight. CHCl3 (400 ml) was added and organic layer washed extensively
with H2O until no peroxide could be found, was dried over MgSO4, filtered and
was treated by chromatography on silica gel to yield 51 g. The product was
dissolved in THF/methanol and saponificated with NaOH and, concentrated to
remove organic solvents at room temperature, added 100 ml H2O, and
extracted with Et2O twice. Organic layer was thoroughly dried and it was left
at room temperature for the next 10 days, then concentrated.
Chromatography on silica gel yielded 13.2 g racemate of lactone - trans-(+/-
)-5-(4-fluorophenyl)-2-(1-methylethyl)-N,4-di-diphenyl-1-[2-(tetrahydro-4-
hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide. This racemate
was divided by chiral synthesis which was made analogously the method in US
Pat. No. 4,581,893. Then each isomer was saponificated with NaOH and
purificated by HPLC. The calcium salt corresponding acid was prepared by
reaction with 1 eq. of CaCl2·2H2O in water.
Brand name
Lipitor
(Pfizer).
Therapeutic Function
Anticholesteremic
General Description
Different sources of media describe the General Description of 134523-00-5 differently. You can refer to the following data:
1. Atorvastatin, [R-(R*,R*)]-2-(4-fluorophenyl)-b,d-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-lH-pyrrole-1-heptanoic acid(Lipitor), also possesses the heptanoic acid side chain,which is critical for inhibition of HMG-CoA reductase.Although the side chain is less lipophilic than the lactoneform, the high amount of lipophilic substitution causes this agent to have a slightly higher level of CNS penetration thanpravastatin, resulting in a slight increase in CNS side effects.Even so, its CNS profile is much lower than that of lovastatin.Atorvastatin is marketed as a combination therapywith amlodipine under the trade name Norvasc for managementof high cholesterol and high blood pressure.
2. Cerivastatin (Baycol) is one of the neweragents in this class of cholesterol-lowering agents. However,it carries a higher incidence of rhabdomyolysis and, as a result,was voluntarily withdrawn from the market by its manufacturerin 2001.
Check Digit Verification of cas no
The CAS Registry Mumber 134523-00-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,4,5,2 and 3 respectively; the second part has 2 digits, 0 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 134523-00:
(8*1)+(7*3)+(6*4)+(5*5)+(4*2)+(3*3)+(2*0)+(1*0)=95
95 % 10 = 5
So 134523-00-5 is a valid CAS Registry Number.
InChI:InChI=1/C33H34FNO5.Ca/c1-21(2)31-30(33(40)24-11-7-4-8-12-24)29(22-9-5-3-6-10-22)32(23-13-15-25(34)16-14-23)35(31)18-17-26(36)19-27(37)20-28(38)39;/h3-16,21,26-27,36-37H,17-20H2,1-2H3,(H,38,39);/q;+2/p-1/t26-,27-;/m1./s1
134523-00-5Relevant articles and documents
[18F]Atorvastatin: synthesis of a potential molecular imaging tool for the assessment of statin-related mechanisms of action
Antunes, Inês F.,Clemente, Gon?alo S.,D?mling, Alexander,Elsinga, Philip H.,Rickmeier, Jens,Ritter, Tobias,Zarganes-Tzitzikas, Tryfon
, (2020/04/24)
Background: Statins are lipid-lowering agents that inhibit cholesterol synthesis and are clinically used in the primary and secondary prevention of cardiovascular diseases. However, a considerable group of patients does not respond to statin treatment, and the reason for this is still not completely understood. [18F]Atorvastatin, the 18F-labeled version of one of the most widely prescribed statins, may be a useful tool for statin-related research. Results: [18F]Atorvastatin was synthesized via an optimized ruthenium-mediated late-stage 18F-deoxyfluorination. The defluoro-hydroxy precursor was produced via Paal-Knorr pyrrole synthesis and was followed by coordination of the phenol to a ruthenium complex, affording the labeling precursor in approximately 10% overall yield. Optimization and automation of the labeling procedure reliably yielded an injectable solution of [18F]atorvastatin in 19% ± 6% (d.c.) with a molar activity of 65 ± 32 GBq·μmol?1. Incubation of [18F]atorvastatin in human serum did not lead to decomposition. Furthermore, we have shown the ability of [18F]atorvastatin to cross the hepatic cell membrane to the cytosolic and microsomal fractions where HMG-CoA reductase is known to be highly expressed. Blocking assays using rat liver sections confirmed the specific binding to HMG-CoA reductase. Autoradiography on rat aorta stimulated to develop atherosclerotic plaques revealed that [18F]atorvastatin significantly accumulates in this tissue when compared to the healthy model. Conclusions: The improved ruthenium-mediated 18F-deoxyfluorination procedure overcomes previous hurdles such as the addition of salt additives, the drying steps, or the use of different solvent mixtures at different phases of the process, which increases its practical use, and may allow faster translation to clinical settings. Based on tissue uptake evaluations, [18F]atorvastatin showed the potential to be used as a tool for the understanding of the mechanism of action of statins. Further knowledge of the in vivo biodistribution of [18F]atorvastatin may help to better understand the origin of off-target effects and potentially allow to distinguish between statin-resistant and non-resistant patients.
Preparation technology of atorvastatin
-
, (2017/08/27)
The invention discloses preparation technology of atorvastatin. The preparation technology comprises the following steps: a first step, the reaction of phenylacetic acid and thionyl chloride is carried out in order to obtain phenylacetyl chloride; a second step, the Friedel-Crafts acylation reaction of phenylacetyl chloride and fluorobenzene is carried out under the action of catalyst, in order to obtain 4-fluorophenyl acetophenone; a third step, 4-fluorophenyl acetophenone is brominated and the brominated 4-fluorophenyl acetophenone is reacted with N-phenyl-isobutyloylacetamide in order to obtain M-4; a fourth step, a reaction is carried out for M-4 and ATS-9 in a cyclohexane, toluene or a mixed solvent of cyclohexane and toluene, pivalic acid is used for catalysis, and a condensation product is obtained. Phenylacetyl chloride and fluorobenzene are reacted in a catalytic action of zeolite molecular sieve, a complexation reaction of the catalyst and products is avoided, reaction yield is improved, and side reactions are few in order to facilitate purification; post-treatment can be carried out for excess M-4 for recycling and reusing, reaction yield is improved, mole proportion of M-4 to ATS-9 and the addition amount of pivalic acid can be adjusted, and final yield of the reaction is improved.
Enantioselective synthesis of allylboronates and allylic alcohols by copper-catalyzed 1,6-boration
Luo, Yunfei,Roy, Iain D.,Madec, Amael G. E.,Lam, Hon Wai
supporting information, p. 4186 - 4190 (2014/05/06)
Chiral secondary allylboronates are obtained in high enantioselectivities and 1,6:1,4 ratios by the copper-catalyzed 1,6-boration of electron-deficient dienes with bis(pinacolato)diboron (B2(pin)2). The reactions proceed efficiently using catalyst loadings as low as 0.0049 mol %. The allylboronates may be oxidized to the allylic alcohols, and can be used in stereoselective aldehyde allylborations. This process was applied to a concise synthesis of atorvastatin, in which the key 1,6-boration was performed using only a 0.02 mol % catalyst loading. 1,6-Borations of electron-deficient dienes with bis(pinacolato)diboron using copper catalyst loadings as low as 0.0049 mol % provided chiral allylboronates that, after oxidation, result in allylic alcohols in high enantioselectivities and 1,6:1,4 ratios. The allylboronates can also be used in stereoselective allylations of aldehydes. This process was applied to a concise synthesis of atorvastatin.
