PYRIDINYLQUINAZOLINAMINE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
申请人:Aquila Brian
公开号:US20100216791A1
公开(公告)日:2010-08-26
The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
Two alternative methods for producing at least one N-substituted acyclic ethylene diamine are provided:
Method A according to the invention comprises:
- reacting at least one reducing sugar, hydrogen and at least one primary amine NH2R or at least one secondary amine NHR'R" or a mixture of at least one primary amine NH2R and at least one secondary amine NHR'R"
- in the presence of a supported hydrogenation catalyst
- at a reaction temperature of 50°C to 200 °C, and
- at a reaction pressure being superatmospheric pressure, and wherein
- the molar ratio of the at least one primary amine and/or secondary amine : reducing sugar is at least 4:1.
Method B according to the invention comprises the steps:
1. reacting at least one reducing sugar and at least one primary amine NH2R or at least one secondary amine NH2R'R" or a mixture of at least one primary amine NH2R and at least one secondary amine NHR'R" in a first step, and
2. reacting the reaction mixture obtained in step 1) with hydrogen in the presence of a supported hydrogenation catalyst in a second step.