81846-19-7

Basic information

• Product Name: REMODULIN
• Synonyms: 2-[[[(1R,2R,3aS,9aS)-2α-Hydroxy-1β-[(S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-benzo[f]indene]-5-yl]oxy]acetic acid;UT-15;[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid;[1R-[1α(S*),2β,3aα,9aα]]-;2-[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-Hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic Acid;Acetic acid, 2-[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]-;Treprostinil Sodium intermediate;REMODULIN
• CAS NO: 81846-19-7
• Molecular Formula: C₂₃H₃₄O₅
• Molecular Weight: 390.51
• EINECS: 1592732-453-0
• Product Categories: Aromatics;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 81846-19-7.mol
• Article Data: 22

Chemical Properties

• Melting Point: 121-123°
• Boiling Point: 587.1 °C at 760 mmHg
• Flash Point: 199.3 °C
• Appearance: /
• Density: 1.158 g/cm³
• Vapor Pressure: 1.25E-14mmHg at 25°C
• Refractive Index: 1.553
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Chloroform (Slightly, Heated), Methanol (Slightly, Heated)
• PKA: 3.19±0.10(Predicted)
• CAS DataBase Reference: REMODULIN(CAS DataBase Reference)
• NIST Chemistry Reference: REMODULIN(81846-19-7)
• EPA Substance Registry System: REMODULIN(81846-19-7)

Safety Data

• Hazardous Substances Data: 81846-19-7(Hazardous Substances Data)

Usage

Uses

Synthetic analog of Prostacyclin (P839060). Antihypertensive. Treprostinil, marketed under the trade name Remodulin is a medication used to treat pulmonary arterial hypertension (PAH).

Pharmacokinetics

Treprostinil is rapidly absorbed from the subcutaneous site of infusion, with an almost 100% bioavailability and a mean half-life of 85 minutes (34 minutes for the IV infusion). The IV solution must be diluted with normal saline or sterile water before starting the infusion. Unlike epoprostenol, treprostinil is stable at room temperature for up to 5 years, with vasodilation action lasting from 4 to 6 hours, compared with the short, 2- to 3-minute action for epoprostenol. Because of its long life in the body, it can be administered under the skin with a microinfusion subcutaneous infusion pump rather than into the bloodstream and, thus, without hospitalization, as contrasted with the central IV infusion of epoprostenol.

Clinical Use

Treprostinil is a synthetic, stable form of prostacyclin for the treatment for advanced pulmonary hypertension with NYHA class III or IV symptoms as well as for late-stage peripheral vascular disease (PVD). Its sodium salt injectable form is administered either as a continuous subcutaneous infusion directly into the skin or, if the subcutaneous infusion is not tolerated, as a continuous IV infusion without an implanted catheter.

Side effects

Side effects include jaw pain, headaches, nausea, diarrhea, flushing, and localized pain at the delivery site under the skin. This pain has been reported as slight to severe irritation. Patients using the drug seem to ex-perience improvement in their condition, including decreased fatigue, decreased shortness of breath, and decreased pulmonary artery pressures, as well as overall improvement in quality of life.

InChI:InChI=1/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1

Upstream product

• 101692-03-9 2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-((3S)-3-hydroxyoctyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetonitrile 
• 6971-51-3 3-methoxybenzyl alcohol 
• 136911-16-5 (2-allyl-3-methoxyphenyl)methanol 
• 153974-48-2 3-methoxy-O-tert-butyldimethylsilylbenzyl alcohol 
• 81007-64-9 (S)-1-chloroheptane-2-ol 
• 94956-98-6 2-allyl-3-methoxybenzaldehyde 
• 223734-55-2 2-allyl-3-methoxy-O-tert-butyldimethylsilylbenzyl alcohol 
• 678992-51-3 (S)-1-chloro-O-tetrahydropyran-2-yl-heptan-2-ol 
• 223734-62-1 2-[[(1S)-1-(3-butynyl)hexyl]oxy]tetrahydro-2H-pyran 
• 678992-52-4 1-(trimethylsilyl)-O-tetrahydropyran-2-yl-1-decyn-5-(S)-ol 
• 101692-01-7 (1R,2R,3aS,9aS)-1-[(3S)-3-hydroxyoctyl]-5-methoxy-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-2-ol 
• 101692-02-8 (1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-1-((S)-3-hydroxyoctyl)-1H-cyclopenta[b]naphthalene-2,5-diol 
• 223734-57-4 (6S)-1-[3-methoxy-2-(2-propenyl)phenyl]-6-[(tetrahydro-2H-pyran-2-yl)oxy]-2-undecyn-1-one 
• 223734-56-3 3-methoxy-2-(2-propenyl)-α-[(5S)-5-[(tetrahydro-2H-pyran-2-yl)oxy]-1-decynyl]benzenemethanol 

Downstream Products

• 830354-48-8 2-(((1R,2R,3aS,9aS)-2-hydroxy-1-((S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl)oxy)acetic acid diethanolamine salt 
• 1422974-92-2 C₃₄H₄₆O₇ 
• 1422974-98-8 C₃₂H₄₄O₇ 
• 1422974-99-9 C₃₇H₅₇NO₇S 
• 1422975-14-1 C₃₇H₅₇NO₇S 
• 81845-98-9 2-((1R,2R,3aS,9aS)-2-hydroxy-1-(S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalene-5-yloxylacetic acid methyl ester 

Relevant articles and documents

EFFICIENT CRYSTALLIZATION PROCESS FOR PREPARING ULTRAPURE TREPROSTINIL AND CRYSTAL PREPARED THEREFROM

There is provided a crystalline Form I of anhydrous Treprostinil and processes for the preparation thereof. The crystalline Form I of anhydrous Treprostnil is a stable crystalline form, which can provide steady physicochemical properties for pharmaceutical formulations, and is advantageous widely and safety used in storage, shipment, and handling for commercially considerations.

Synthesis of treprostinil: Key claisen rearrangement and catalytic pauson-khand reactions in continuous flow

A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson-Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection-deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin.

Intermediate for preparing treprostinil, preparation method of intermediate and method for preparing treprostinil through intermediate

The invention relates to an intermediate for preparing treprostinil, a preparation method of the intermediate and a method for preparing the treprostinil through the intermediate. Specifically, the invention relates to a compound which is shown as a formula (VI) and is used for preparing the treprostinil (shown as a formula (I)), a preparation method of the compound and a method for preparing the treprostinil through the compound. The method for preparing the treprostinil comprises the following steps: carrying out reduction and hydroxyl removal protection on the compound shown as the formula (VI) to obtain a compound shown as a formula (III); taking the compound shown as the formula (III) and chloroacetonitrile to react and hydrolyzing to prepare the treprostinil shown as the formula (I). The method is simple and convenient to operate, high in synthesis yield and suitable for large-scale production. (The formula (I) is shown in the description, the formula (III) is shown in the description and the formula (VI) is shown in the description.).