Provided herein are synthetic methods for the preparation of intermediates that are utilized in the synthesis of omecamtiv mecarbil dihydrochloride.

Provided herein are synthetic methods for the preparation of intermediates that are utilized in the synthesis of omecamtiv mecarbil dihydrochloride.

The present invention refers to a crystalline 2-fluoro-3-nitrotoluene compound of formula (I), and a process for the preparation thereof. Furthermore, the present invention relates to a process for the synthesis of a compound of formula (II) or salts thereof by means of the crystalline 2-fluoro-3-nitrotoluene.

##STR00001##

The present invention refers to a crystalline 2-fluoro-3-nitrotoluene compound of formula (I), and a process for the preparation thereof. Furthermore, the present invention relates to a process for the synthesis of a compound of formula (II) or salts thereof by means of the crystalline 2-fluoro-3-nitrotoluene.

##STR00001##

The present invention refers to a crystalline 2-fluoro-3-nitrotoluene compound of formula (I), and a process for the preparation thereof. Furthermore, the present invention relates to a process for the synthesis of a compound of formula (II) or salts thereof by means of the crystalline 2-fluoro-3-nitrotoluene.

##STR00001##

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure ArOH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure ArOH to provide a fluorinated aryl species having the structure ArF.

Disclosed is a fluorination method comprising providing an aryl fluorosulfonate and a fluorinating reagent to a reaction mixture; and reacting the aryl fluorosulfonate and the fluorinating reagent to provide a fluorinated aryl species. Also disclosed is a fluorination method comprising providing, a salt comprising a cation and an aryloxylate, and SO.sub.2F.sub.2 to a reaction mixture; reacting the SO.sub.2F.sub.2 and the ammonium salt to provide a fluorinated aryl species. Further disclosed a fluorination method comprising providing a compound having the structure ArOH to a reaction mixture; where Ar is an aryl or heteroaryl; providing SO.sub.2F.sub.2 to the reaction mixture; providing a fluorinating reagent to the reaction mixture; reacting the SO.sub.2F.sub.2, the fluorinating reagent and the compound having the structure ArOH to provide a fluorinated aryl species having the structure ArF.

The invention relates to a use of a fluorination gas, and the elemental fluorine (F.sub.2) is present in a high concentration, for example, in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15 or even 20% by volume, and to a process for the manufacture of a fluorinated compound by direct fluorination employing a fluorination gas, wherein the elemental fluorine (F.sub.2) is present in a high concentration. The process of the invention is directed to the manufacture of a fluorinated compound, for the exception of fluorinated benzene, by direct fluorination. Especially the invention is of interest in the preparation of fluorinated organic compounds, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications. The fluorination process of the invention may be performed batch-wise or in a continuous manner.

The invention relates to a use of a fluorination gas, and the elemental fluorine (F.sub.2) is present in a high concentration, for example, in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15 or even 20% by volume, and to a process for the manufacture of a fluorinated compound by direct fluorination employing a fluorination gas, wherein the elemental fluorine (F.sub.2) is present in a high concentration. The process of the invention is directed to the manufacture of a fluorinated compound, for the exception of fluorinated benzene, by direct fluorination. Especially the invention is of interest in the preparation of fluorinated organic compounds, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications. The fluorination process of the invention may be performed batch-wise or in a continuous manner.

The invention relates to a use of a fluorination gas, wherein the elemental fluorine (F.sub.2) is present in a high concentration, for example, in a concentration of elemental fluorine (F.sub.2), especially of equal to much higher than 15% or even 20% by volume (i.e., at least 15% or even 20% by volume), and to a process for the manufacture of a fluorinated benzene by direct fluorination employing a fluorination gas, wherein the elemental fluorine (F.sub.2) is present in a high concentration. The process of the invention is directed to the manufacture of a fluorinated benzene by direct fluorination. Especially the invention is of interest in the preparation of fluorinated benzene, final products and as well intermediates, for usage in agro-, pharma-, electronics-, catalyst, solvent and other functional chemical applications. The fluorination process of the invention may be performed batch-wise or in a continuous manner. If the process of the invention is performed batch-wise, a column (tower) reactor may be used. If the process of the invention is continuous a microreactor may be used. The invention is characterized in that the starting compound is benzene, and the fluorinated compound produced is a fluorinated benzene, preferably monofluorobenzene.