Treprostinil diolamine

Base Information

• Chemical Name: Treprostinil diolamine
• CAS No.: 830354-48-8
• Molecular Formula: C₄H₁₁NO₂*C₂₃H₃₄O₅
• Molecular Weight: 495.657
• UNII: H1FKG90039
• DSSTox Substance ID: DTXSID50232132
• Wikidata: Q27279501
• NCI Thesaurus Code: C152730
• ChEMBL ID: CHEMBL2107815
• Mol file: 830354-48-8.mol

Synonyms:((1R,2R,3AS,9AS)-2-hydroxy-1-((3S)-3-hydroxyoctyl)-2,3,3A,4,9,9A-hexahydro-1H-cylopent(b)naphthalen-5-yl)oxy)acetate;Orenitram;Remodulin;trepostinil sodium;treprostinil;treprostinil diethanolamine;treprostinil diolamin;treprostinil diolamine;treprostinil sodium;UT-15;UT-15C

Chemical Property of Treprostinil diolamine

Chemical Property:

• Hydrogen Bond Donor Count: 6
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 14
• Exact Mass: 495.31960277
• Heavy Atom Count: 35
• Complexity: 524

Purity/Quality:

95% by HPLC ^*data from raw suppliers

TreprostinilDiolamine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCCCCC(CCC1C(CC2C1CC3=C(C2)C(=CC=C3)OCC(=O)O)O)O.C(CO)NCCO
• Isomeric SMILES: CCCCC[C@@H](CC[C@H]1[C@@H](C[C@H]2[C@@H]1CC3=C(C2)C(=CC=C3)OCC(=O)O)O)O.C(CO)NCCO
• Recent ClinicalTrials: Telemonitoring to Treat Group 2 Pulmonary Hypertension
• Recent EU Clinical Trials: A Phase III, International, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Clinical Worsening Study of UT-15C in Subjects with Pulmonary Arterial Hypertension Receiving Background Oral Monotherapy.
• Uses: Treprostinil Diolamine is a sustained-release oral formulation of Treprostinil (T719500) and was studied to determine whether it could provide a more convenient prostacyclin treatment option for patients with less severe pulmonary arterial hypertension.Treprostinil Diolamine is an sustained-release oral prostacyclin analog and was studied to determine pharmacokinetic profile in PAH patients after chronic dosing,

Technology Process of Treprostinil diolamine

There total 11 articles about Treprostinil diolamine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.0%

2,2'-iminobis[ethanol] (111-42-2) + treprostinil (81846-19-7) → 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 (830354-48-8)

Guidance literature:

In methanol; at 25 - 35 ℃; for 0.5h; Temperature; Solvent;

Reference yield:

methyl 2-hydroxy-5-methoxy-3,4-dihydronaphthalene-1-carboxylate (99511-79-2) → 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 (830354-48-8)

Guidance literature:

Multi-step reaction with 13 steps

1.1: diisopropylamine; n-butyllithium / tetrahydrofuran; hexane / 1 h / -60 °C

1.2: 22 h / 5 - 20 °C

2.1: lithium chloride / water; N,N-dimethyl acetamide / 2 h / 100 °C

3.1: acetic anhydride; triethylamine / dichloromethane / 1 h / 20 °C

4.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -60 °C

4.2: 2 h / -60 °C

4.3: 1 h

5.1: potassium carbonate; palladium 10% on activated carbon; hydrogen / ethanol / 7 h / 20 °C / 2585.81 Torr

6.1: sodium hydroxide; water / ethanol / 0.5 h / -10 °C

6.2: 3 h / -10 °C

7.1: toluene-4-sulfonic acid / methanol / 2 h / 20 °C

8.1: lipase AK (Amano) / hexane / 22 h / 20 °C / Enzymatic reaction

9.1: potassium hydroxide; water / methanol / 5 h / Reflux

10.1: n-butyllithium; diphenylphosphane / tetrahydrofuran; hexane / 19 h / Reflux

11.1: potassium carbonate / acetone / 8 h / Reflux

12.1: potassium hydroxide; water / methanol / 2 h / Reflux

13.1: ethanol; ethyl acetate / 0.5 h / 70 °C

13.2: polymorph B of treprostinil diethanolamine / 17 h / 20 - 50 °C

With n-butyllithium; lipase AK (Amano); palladium 10% on activated carbon; water; hydrogen; acetic anhydride; potassium carbonate; toluene-4-sulfonic acid; triethylamine; diisopropylamine; diphenylphosphane; lithium chloride; potassium hydroxide; sodium hydroxide; In tetrahydrofuran; methanol; ethanol; hexane; dichloromethane; N,N-dimethyl acetamide; water; ethyl acetate; acetone;

Reference yield:

C15H16O6 → 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 (830354-48-8)

Guidance literature:

Multi-step reaction with 12 steps

1.1: lithium chloride / water; N,N-dimethyl acetamide / 2 h / 100 °C

2.1: acetic anhydride; triethylamine / dichloromethane / 1 h / 20 °C

3.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -60 °C

3.2: 2 h / -60 °C

3.3: 1 h

4.1: potassium carbonate; palladium 10% on activated carbon; hydrogen / ethanol / 7 h / 20 °C / 2585.81 Torr

5.1: sodium hydroxide; water / ethanol / 0.5 h / -10 °C

5.2: 3 h / -10 °C

6.1: toluene-4-sulfonic acid / methanol / 2 h / 20 °C

7.1: lipase AK (Amano) / hexane / 22 h / 20 °C / Enzymatic reaction

8.1: potassium hydroxide; water / methanol / 5 h / Reflux

9.1: n-butyllithium; diphenylphosphane / tetrahydrofuran; hexane / 19 h / Reflux

10.1: potassium carbonate / acetone / 8 h / Reflux

11.1: potassium hydroxide; water / methanol / 2 h / Reflux

12.1: ethanol; ethyl acetate / 0.5 h / 70 °C

12.2: polymorph B of treprostinil diethanolamine / 17 h / 20 - 50 °C

With n-butyllithium; lipase AK (Amano); palladium 10% on activated carbon; water; hydrogen; acetic anhydride; potassium carbonate; toluene-4-sulfonic acid; triethylamine; diphenylphosphane; lithium chloride; potassium hydroxide; sodium hydroxide; In tetrahydrofuran; methanol; ethanol; hexane; dichloromethane; N,N-dimethyl acetamide; water; ethyl acetate; acetone;

upstream raw materials:

2,2'-iminobis[ethanol]

treprostinil

methyl 2-hydroxy-5-methoxy-3,4-dihydronaphthalene-1-carboxylate

5-Methoxy-2-oxo-1,2,3,4-tetrahydronaphthalen-3-ylacetic acid

Downstream raw materials:

treprostinil