138530-94-6

Basic information

• Product Name: R-(+)-Lansoprazole
• Synonyms: (R)-2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazole;1H-Benzimidazole, 2-[(R)-[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]- (9CI);1H-Benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-, (R)-;R-(+)-Lansoprazole;Dexlansoprazole;2-[(R)-[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole;T 168390;TAK 390
• CAS NO: 138530-94-6
• Molecular Formula: C₁₆H₁₄F₃N₃O₂S
• Molecular Weight: 369.36
• EINECS: 1308068-626-2
• Product Categories: Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;APIs;DEXILANT
• Mol File: 138530-94-6.mol
• Article Data: 38

Chemical Properties

• Melting Point: 66-68?C
• Boiling Point: 555.8±60.0 °C(Predicted)
• Appearance: Brown solid
• Density: 1.50±0.1 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 9.56±0.10(Predicted)
• Stability: Hygroscopic
• CAS DataBase Reference: R-(+)-Lansoprazole(CAS DataBase Reference)
• NIST Chemistry Reference: R-(+)-Lansoprazole(138530-94-6)
• EPA Substance Registry System: R-(+)-Lansoprazole(138530-94-6)

Safety Data

• Hazardous Substances Data: 138530-94-6(Hazardous Substances Data)

Usage

Description

R-(+)-Lansoprazole, also known as the R-enantiomer of Lansoprazole, is a gastric proton pump inhibitor and an antiulcerative agent. It is an enantiomerically pure form of lansoprazole, which is a proton pump inhibitor that irreversibly inactivates the H+/K+-stimulated ATPase pumps in parietal cells, inhibiting gastric acid secretion and increasing intragastric pH. R-(+)-Lansoprazole is a brown solid and is available under the brand name Kapidex.

Uses

Used in Pharmaceutical Industry:
R-(+)-Lansoprazole is used as a gastric proton pump inhibitor for the treatment of various diseases requiring acid suppression, such as heartburn, peptic ulcers, and gastroesophageal reflux disease (GERD). It acts by irreversibly binding to the hydrogen/potassium adenosine triphosphatase enzyme system, commonly referred to as the gastric proton pump, of the gastric parietal cell, effectively treating these conditions.
Used in Antiulcer Applications:
R-(+)-Lansoprazole is used as an antiulcerative agent, helping to reduce the formation of ulcers in the stomach and duodenum by inhibiting gastric acid secretion. This makes it a valuable component in the treatment and management of ulcerative conditions.

Originator

Takeda (Japan)

Clinical Use

Takeda Pharmaceuticals received approval of dexlansoprazole, a dual release formulation of the (R)-isomer of lansoprazol proton pump inhibitor (PPI) already in the market, from the FDA in January 2009. Dexlansoprazole is a delayed release capsule for the oncedaily, oral treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD), the healing of erosive esophagitis (EE) and the maintenance of healed EE. The dual release formulation is designed to provide two separate releases of medication, one at 1–2 h and then another at 4–5 h after treatment, for extended efficacy in the treatment of GERD.

Side effects

The most commonly recorded adverse reactions that occurred at a higher incidence than placebo were diarrhea, abdominal pain, nausea, vomiting, flatulence, and upper respiratory tract infection. As dexlansoprazole inhibits gastric acid secretion, its use is expected to interfere with the absorption of drugs with pH-dependent oral bioavailability. Since the HIV protease inhibitor atazanavir is dependent on gastric acid for absorption, dexlansoprazole should not be co-administered with atazanavir to avoid a loss of therapeutic efficacy. While co-administration of dexlansoprazole did not affect the pharmacokinetics of warfarin or INR (international normalized ratio: the ratio of a patient s prothrombin time to a normal sample), there have been reports of increased INR and prothrombin time in patients receiving concomitant treatment with PPIs and warfarin. Since increases in INR and prothrombin time may lead to abnormal bleeding and possibly death, concomitant use of dexlansoprazole and warfarin may necessitate monitoring for increases in INR and prothrombin time.

Synthesis

Similar to the synthesis of the chiral sulfoxide of armodafinil vide supra, the preparation of the chiral sulfoxide of lansoprazole utilized the catalytic oxidation method developed by Kagan and co-workers (the Scheme). Two routes have been reported that describe the preparation of dexlansoprazole on large scale. The first route developed by Takeda reacts commercially available thioether 29, also used to make lansoprazole, under the Kagan asymmetric oxidation conditions and the alternative route utilizes the cheaper commercial intermediate nitrosulfide 30 in the analogous asymmetric oxidation by Kagan). Thus, the catalyst complex consisting of (+)-DET, Ti(OiPr)4 and water was formed in the presence of thioether 29 in toluene at 30–40°C. The reaction mixture was then cooled to 5 °C and DIPEA and cumene hydroperoxide (CMHP) were added to give, after aqueous work-up and in situ crystallization from the organic layer, dexlansoprazole (VI) in 98% ee. No yield was given in the patent. An alternate, but similar, sequence was also described wherein the nitrosulfide intermediate 30 was subjected to similar oxidative conditions that gave intermediate nitro compound 31 in 80% yield and 98% ee. Compound 31 was treated with KOH and trifluoroethanol to provide dexlansoprazole (VI).

InChI:InChI=1/C16H14F3N3O2S/c1-10-13(20-7-6-14(10)24-9-16(17,18)19)8-25(23)15-21-11-4-2-3-5-12(11)22-15/h2-7H,8-9H2,1H3,(H,21,22)/t25-/m1/s1

Upstream product

• 103577-40-8 lansoprazole sulfide 
• 103577-45-3 lansoprasole 
• 853950-77-3 (R)-(+)-2-(3-methyl-4-nitropyridin-2-ylmethansulfinyl)-1H-benzimidazole 
• 75-89-8 2,2,2-trifluoroethanol 
• 134469-07-1 Benzimidazol-2-thiol 
• 1240684-26-7 N-camphorsulfonyl-2-[(R)-[[3-methyl-4-(2,2,2-trifIuoroethoxy)-2-pyridinyl]methyl]sulphinyl]-1H-benzimidazole 
• 152402-98-7 2-[(4-nitro-3-methylpyridin-2-yl)methylsulfanyl]-1H-benzoimidazole 
• 103577-66-8 2-Hydroxymethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine 

Downstream Products

• 503833-43-0 isopropyl 1-[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazol-l-yl] ethyl carbonate 
• 503833-39-4 cyclohexyl 1-[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]ethyl carbonate 
• 503833-38-3 cyclohexyl 1-[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]ethyl carbonate 
• 635751-28-9 2-[methyl[[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]carbonyl]amino]ethyl 4-trifluoromethoxybenzoate 
• 635751-30-3 2-[methyl[[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]carbonyl]amino]ethyl 3,4,5-trimethoxybenzoate 
• 635751-42-7 2-[Cyclohexyl[[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl] sulfinyl]-1H-benzimidazol-1-yl]carbonyl]amino]ethyl ethyl carbonate 
• 635751-84-7 2-[[4-(aminocarbonyl)phenyl] [[(R)-2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl]-1H-benzimidazol-1-yl]carbonyl]amino]ethyl acetate 

Relevant articles and documents

Two-dimensional chromatography method applied to the enantiomeric determination of lansoprazole in human plasma by direct sample injection

A two-dimensional HPLC method based on the direct injection of biological samples has been developed and validated for the determination of lansoprazole enantiomers in human plasma. The lansoprazole enantiomers were extracted from the biological matrix using an octyl restricted access media bovine serum albumin column (C8 RAM BSA) and the enantioseparation was performed on an amylose tris(3,5-dimethoxyphenylcarbamate) chiral column using acetonitrile:water (35:65 v/v) and UV detection at 285 nm. Analysis time was 25 min with no time spent on sample preparation. The method was applied to the analysis of the plasma samples obtained from nine Brazilian volunteers who received a 30 mg oral dose of racemic lansoprazole and was able to quantify the enantiomers of lansoprazole in the clinical samples analyzed.

Preparation method of high-optical-purity anti-gastric-ulcer drug R-lansoprazole

The invention belongs to the technical field of chiral synthesized chemical drugs and in particular relates to a preparation method of a high-optical-purity anti-gastric-ulcer drug R-lansoprazole. According to the preparation method, a molecular sieve is used as a carrier and tungsten trioxide is loaded on the surface of the molecular sieve in situ to prepare a tungsten loaded molecular sieve; L-hydroxyproline and tetraisopropyl titanate form a complex compound and the complex compound is deposited on the surface of the tungsten loaded molecular sieve and/or in a pore diameter to form a tungsten-titanium double-metal center catalyst; the catalyst can be used for catalyzing thioether2-[3-methyl-4-(2,2,2-trifluoroethoxy)pyridine-2-yl]-methylthio-1H-benzimidazole to be subjected to oxidization reaction to obtain the high-optical-purity R-lansoprazole; the chemical purity and optical purity of the prepared product reach requirements of medical-grade crude drugs.

Ultrafast chiral separations for high throughput enantiopurity analysis

Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.