The invention provides a composition of matter which:

(i) consists of at least 90% by weight of an atropisomer (2A) and 0-10% by weight of an atropisomer of formula (2B); or
(ii) consists of at least 90% by weight of an atropisomer (2B) and 0-10% by weight of an atropisomer of formula (2A);
wherein the atropisomer of formula (2A) and the atropisomer of formula (2B) are represented by:

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or are pharmaceutically acceptable salts or tautomers thereof, wherein ring X is a benzene or pyridine ring; ring Y is selected from a benzene ring, a pyridine ring and a thiophene ring; R.sup.1 is trifluoromethyl; R.sup.2 is hydrogen; R.sup.3 is hydrogen; m is 0 or 1; n is 0, 1 or 2; Ar.sup.1 is a monocyclic aromatic ring selected from benzene and pyridine; each monocyclic aromatic ring being unsubstituted or substituted with 1 or 2 substituents R.sup.5 as defined herein; and R.sup.4; R.sup.5 when present, R.sup.6 and R.sup.7 independently selected from various substituents as defined herein.

Also provided are individual atropisomers, pharmaceutical compositions and the uses of the atropisomers and compositions are inhibitors of PLK1- and PLK4 kinases, for example in the treatment of cancers.

The invention discloses a method for preparations of fluoro, chloro and fluorochloro alkylated compounds by homogeneous Pd catalyzed fluoro, chloro and fluorochloro alkylation with fluoro, chloro and fluorochloroalkyl halides in the presence of di(1-adamantyl)-adamantyl-n-butylphosphine and in the presence of 2,2,6,6-tetramethylpiperdine 1-oxyl.

The invention discloses a method for preparations of fluoro, chloro and fluorochloro alkylated compounds by homogeneous Pd catalyzed fluoro, chloro and fluorochloro alkylation with fluoro, chloro and fluorochloroalkyl halides in the presence of di(1-adamantyl)-adamantyl-n-butylphosphine and in the presence of 2,2,6,6-tetramethylpiperdine 1-oxyl.

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

The invention relates to a new process for producing useful intermediates for the manufacture of NEP inhibitors or prodrugs thereof, in particular NEP inhibitors comprising a γ-amino-δ-biphenyl-α-methylalkanoic acid, or acid ester, backbone, such as N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester or salt thereof.

Disclosed are a method for producing a highly reactive intermediate, which comprises: preparing an electron-accepting active compound (1), preparing a piezoelectric material (3), and applying mechanical strain to the piezoelectric material (3) in the presence of the electron-accepting active compound (1) and the piezoelectric material (3), and subjecting the compound (1) to one-electron reduction to generate a corresponding highly reactive intermediate; a redox reaction method using the method for producing the same; and a method for producing a redox reaction product.

The invention discloses a method for the preparation of fluoro alkylated compounds by homogeneous Ni catalyzed fluoro alkylation with fluoro alkyl halides in the presence of a base.

The invention discloses a method for the preparation of fluoro alkylated compounds by homogeneous Ni catalyzed fluoro alkylation with fluoro alkyl halides in the presence of a base.

The present technology provides compounds according to Formula I or Formula III as well as compositions including such compounds useful for the treatment of metastatic cancer and/or glaucoma.

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The invention discloses a method for the preparation of fluoro alkylated compounds by homogeneous Ni catalyzed fluoro alkylation with fluoro alkyl halides in the presence of a base.