1393813-42-7

Basic information

• Product Name: SulfaMide, N-[5-(4-broMophenyl)-6-chloro-4-pyriMidinyl]-N'-propyl-
• Synonyms: SulfaMide, N-[5-(4-broMophenyl)-6-chloro-4-pyriMidinyl]-N'-propyl-;N-[5-(4-broMophenyl)-6-chloro-4-pyriMidinyl]-N'-propyl-SulfaMide;N-(5-(4-bromophenyl)-6-chloropyrimidin-4-yl)propane-1-sulfamide;5-(4-bromophenyl)-6-chloro-N-(propylsulfamoyl)pyrimidin-4-amine;N-[5-(4-Bromphenyl)-6-chlorpyrimidin-4-yl]-N'-propylsulfamid
• CAS NO: 1393813-42-7
• Molecular Formula: C₁₃H₁₄BrClN₄O₂S
• Molecular Weight: 405.69786
• Mol File: 1393813-42-7.mol

Chemical Properties

• Boiling Point: 518.2±60.0 °C(Predicted)
• Appearance: /
• Density: 1.612±0.06 g/cm3(Predicted)
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly)
• PKA: 4.75±0.50(Predicted)
• CAS DataBase Reference: SulfaMide, N-[5-(4-broMophenyl)-6-chloro-4-pyriMidinyl]-N'-propyl-(CAS DataBase Reference)
• NIST Chemistry Reference: SulfaMide, N-[5-(4-broMophenyl)-6-chloro-4-pyriMidinyl]-N'-propyl-(1393813-42-7)
• EPA Substance Registry System: SulfaMide, N-[5-(4-broMophenyl)-6-chloro-4-pyriMidinyl]-N'-propyl-(1393813-42-7)

Safety Data

• Hazardous Substances Data: 1393813-42-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
SulfaMide, N-[5-(4-bromophenyl)-6-chloro-4-pyrimidinyl]-N'-propylis used as a synthetic intermediate for the production of Macitentan (M105005). Macitentan is an orally active, potent dual endothelin receptor antagonist that is specifically designed to treat pulmonary arterial hypertension. The compound's unique structure allows it to effectively block the action of endothelin, a potent vasoconstrictor, thereby reducing the pressure in the pulmonary arteries and improving the symptoms of pulmonary arterial hypertension.
Application Reason:
The use of SulfaMide, N-[5-(4-bromophenyl)-6-chloro-4-pyrimidinyl]-N'-propylin the synthesis of Macitentan is due to its ability to provide a stable and efficient route for the production of the drug. The compound's unique chemical structure allows for the formation of the desired drug with high selectivity and yield, making it an essential component in the pharmaceutical industry.

Upstream product

• 1878-68-8 2-(4-bromophenyl)-acetic acid 
• 41841-16-1 (4-bromo-phenyl)-acetic acid methyl ester 
• 149506-35-4 2-(4-bromophenyl)-malonic acid dimethyl ester 
• 706811-25-8 5-(4-bromophenyl)-4,6-dihydroxypyrimidine 
• 146533-41-7 5-(4-bromophenyl)-4,6-dichloropyrimidine 
• 147962-41-2 N-propylaminosulfonamide 

Downstream Products

• 1393813-43-8 N‐[5‐(4‐bromophenyl)‐6‐[2‐hydroxyethoxy]‐4‐pyrimidinyl]‐N‐propylsulfamide 
• 1433875-21-8 ACT-080803 
• 2211059-05-9 2‐((6‐amino‐5‐(4‐bromophenyl)pyrimidin‐4‐yl)oxy)ethan‐1‐ol 

Relevant articles and documents

Improved and single-pot process for the synthesis of macitentan, an endothelin receptor antagonist, via lithium amide-mediated nucleophilic substitution

Abstract: An improved, simple, efficient, and telescoped synthesis of macitentan, an endothelin receptor antagonist, starting from 5-(4-bromophenyl)-4,6-dichloropyrimidine in an overall yield of around 62% is described. Graphical abstract: [Figure not available: see fulltext.].

METHOD FOR PREPARING MACITENTAN AND INTERMEDIATE COMPOUND THEREOF

The present invention relates to technical field of chemical synthesis of drugs, and provides a preparation method of Macitentan and intermediate compound thereof. Adding. THF solution containing compound II and 5-bromo-2-chloropyrimidine slowly into THF

PROCESS FOR PREPARING AN ENDOTHELIN RECEPTOR ANTAGONIST

The present invention relates to a process for preparing macitentan of Formula (I): to macitentan prepared according to such a process and to macitentan in substantially pure form.

PROCESS FOR PREPARATION OF MACITENTAN

The present invention relates to a process for the preparation of N-[5-(4-Bromophenyl)- 6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'propylsulfamide or Macitentan of Formula (I). The present invention further relates to a process for the preparation highly pure N-[5- (4-Bromophenyl)-6- [2- [(5 -bromo-2-pyrimidinyl)oxy]ethoxy] -4-pyrimidinyl] - N'propylsulfamide or Macitentan of Formula (I). Said substantially pure Macitentan is useful in the preparation of pharmaceutical composition for the treatment of cardiac disorders.

AN IMPROVED PROCESS FOR THE PREPARATION OF MACITENTAN

The present invention relates to an improved process for the preparation of macitentan and pharmaceutical acceptable salts thereof. Further present invention also relates to methylene chloride solvate of macitentan and their use in the preparation of pure macitentan.

PROCESS FOR THE PREPARATION OF MACITENTAN AND INTERMEDIATES THEREOF

The present invention relates to an improved process for preparation of Macitentan and intermediates thereof. The present invention also relates to a novel ammonium salt of Macitentan. The present invention further relates to a process for the preparation of amorphous Macitentan.

PROCESS FOR PREPARING A PYRIMIDINE INTERMEDIATE

The present invention relates to a process for preparing a pyrimidine intermediate, namely the compound of formula I-2 or a salt thereof. Said compound of formula I-2 or its salt can be used to prepare macitentan. Macitentan (chemical names: N-[5-(4-bromophenyl)-6-[2-[(5-bromo- 2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl] -N'-propylsulfamide or N-[5-(4-bromophenyl)- 6- {2- [(5 -bromopyrimidin-2-yl)oxy] ethoxy } pyrimidin-4-yl] -N'-propylsulfuric diamide) is an endothelin receptor antagonist that has notably been approved by the US Food and Drug Administration and the European Commission for the treatment of pulmonary arterial hypertension. It has been first disclosed in WO 02/053557. The last step of one of the potential preparation routes described in WO 02/053557, called Possibility A and Possibility B , can be summarised as shown in Scheme Al hereafter.

PREPARATION OF PYRIMIDINE INTERMEDIATES USEFUL FOR THE MANUFACTURE OF MACITENTAN

The present invention relates to a new synthetic intermediate, namely the compound of formula I-2 I or a salt thereof. Said compound of formula I-2 or its salt can be used to prepare the compound of formula I-3 I which is an important synthetic intermediate used in the preparation of macitentan.

The discovery of N -[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy] ethoxy]-4-pyrimidinyl]- N ′-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist

Starting from the structure of bosentan (1), we embarked on a medicinal chemistry program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ETA with significant affinity for the ET B receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clinical trial for pulmonary arterial hypertension.