The invention provides a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, especially KRAS G12C inhibitors. The present invention provides a direct enantioselective chemical manufacturing method of making Compound A, or a pharmaceutically acceptable hydrate or solvent thereof: (I). The invention provides a process for preparing Intermediate B6* comprising reacting Intermediate B4* with Intermediate B5* in an atroposelective coupling reaction, using a chiral catalyst.

##STR00001##

Chemical processes are disclosed that react iron tetracarbonyl dichloride with an alkyl phosphate producing carbon monoxide and a compound represented by the formula FeCl.sub.2(OP(OR).sub.3).sub.n where n is an integer. Simultaneously or subsequently an alkene with carbon tetrachloride may be reacted in the presence of the compound represented by the formula FeCl.sub.2(OP(OR).sub.3).sub.n where n is an integer to produce a chlorinated hydrocarbon.

The present patent application relates to new palladium complexes, to processes for their preparation, and to their use.

In one aspect, phosphine compounds comprising three adamantyl moieties (PAd.sub.3) and associated synthetic routes are described herein. Each adamantyl moiety may be the same or different. For example, each adamantyl moiety (Ad) attached to the phosphorus atom can be independently selected from the group consisting of adamantane, diamantane, triamantane and derivatives thereof. Transition metal complexes comprising PAd.sub.3 ligands are also provided for catalytic synthesis including catalytic cross-coupling reactions.

In one aspect, phosphine compounds comprising three adamantyl moieties (PAd.sub.3) and associated synthetic routes are described herein. Each adamantyl moiety may be the same or different. For example, each adamantyl moiety (Ad) attached to the phosphorus atom can be independently selected from the group consisting of adamantane, diamantane, triamantane and derivatives thereof. Transition metal complexes comprising PAd.sub.3 ligands are also provided for catalytic synthesis including catalytic cross-coupling reactions.

The invention relates to novel processes for manufacturing 6-[[5-methyl-3-(6-methyl-3-pyridyl)isoxazol-4-yl]methoxy]-N-tetrahydropyran-4-yl-pyridazine-3-carboxamide (1), or a pharmaceutically acceptable salt thereof. The processes according to the invention are particularly suitable for large-scale manufacturing of the compound of formula 1 under GMP conditions.

##STR00001##

The invention relates to processes for the synthesis of 2-(3-cyano-5-fluorophenyl)-2-methylpropanoic acid and its use as intermediate in the preparation of GLP-1R/GIPR agonists. The invention also relates to a process of preparing a GLP-1R/GIPR agonist.