The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.

The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.

The present invention relates to an improved asymmetric synthesis of azaspiro or diazaspiro compound (hereafter referred to as the compound 5, (5.sup.A) or (5.sup.N)) or their pharmaceutically acceptable salts and derivatives; through the formation of intermediate compounds 4, (4.sup.A) or (4.sup.N) respectively. The process comprises an unusual substrate specific highly diastereoselective as well as enantio-enriched 1-substituted 2-azaspiro[3.3]heptane or 1-substituted 2-diazaspiro[3.3]heptane compounds with high diastereoselectivity by addition of a cyclobutane carboxylate anion to a Davis-Ellman's imine, followed by reduction and cyclisation resulting in the selective formation of azaspiro or diazaspiro intermediate compound 4, (4.sup.A) or (4.sup.N); which on subsequently removing the sulfinyl group provides corresponding azaspiro or diazaspiro compound 5, (5.sup.A) or (5.sup.N) respectively.

The present invention relates to an improved asymmetric synthesis of azaspiro or diazaspiro compound (hereafter referred to as the compound 5, (5.sup.A) or (5.sup.N)) or their pharmaceutically acceptable salts and derivatives; through the formation of intermediate compounds 4, (4.sup.A) or (4.sup.N) respectively. The process comprises an unusual substrate specific highly diastereoselective as well as enantio-enriched 1-substituted 2-azaspiro[3.3]heptane or 1-substituted 2-diazaspiro[3.3]heptane compounds with high diastereoselectivity by addition of a cyclobutane carboxylate anion to a Davis-Ellman's imine, followed by reduction and cyclisation resulting in the selective formation of azaspiro or diazaspiro intermediate compound 4, (4.sup.A) or (4.sup.N); which on subsequently removing the sulfinyl group provides corresponding azaspiro or diazaspiro compound 5, (5.sup.A) or (5.sup.N) respectively.

A method for the synthesis of diazabicyclo[6.2.0]decane compounds is provided. The synthesis proceeds by stereoselective synthesis of a chiral lactone followed by azetidine formation via a series of chemoselective reactions. Bicyclization results with the formation of diazobicyclo[6.2.0]decane related compounds.

The present invention relates to an improved asymmetric synthesis of alpha-(diarylmethyl) alkyl amines (hereafter referred to as the compound (1)) or its pharmaceutically acceptable salt and derivatives. The process comprises an unusual substrate specific regioselective lithiation of alpha-diarylmethanes. followed by its highly diastereoselective addition to N-tert-butanesulfinylimines resulting in the selective formation of chiral alpha-(diarylmethyl) alkyl amines 4 and chiral amine 5; which on subsequently removing the sulfinyl group provides corresponding alpha-(diarylmethyl) alkyl amines (1) or relative chiral amines (1″).

The present invention relates to an improved asymmetric synthesis of alpha-(diarylmethyl) alkyl amines (hereafter referred to as the compound (1)) or its pharmaceutically acceptable salt and derivatives. The process comprises an unusual substrate specific regioselective lithiation of alpha-diarylmethanes. followed by its highly diastereoselective addition to N-tert-butanesulfinylimines resulting in the selective formation of chiral alpha-(diarylmethyl) alkyl amines 4 and chiral amine 5; which on subsequently removing the sulfinyl group provides corresponding alpha-(diarylmethyl) alkyl amines (1) or relative chiral amines (1″).

The present invention relates to an improved asymmetric synthesis of alpha-branched amines (hereafter referred to as the compound) and relative chiral amines (1″) or its pharmaceutically acceptable salt and derivatives. The process comprises an unusual substrate specific regioselective ortho lithiation of substituted arene compounds, followed by its highly diastereoselective addition to N-tert-butanesulfinylimines resulting in the selective formation of alpha-branched sulfinyl amine and chiral amine; which on subsequently removing the sulfinyl group provides corresponding alpha-branched amines or relative chiral amines (1″).

The present invention relates to an improved process for diastereoselective synthesis of vicinal diamines (1). The process involves highly regio- and diastereoselective addition of 2-azaallyl anions (4) to N-tert-butanesulfinylimines (5) to produce vicinal diamines (1).

The present invention relates to an improved process for diastereoselective synthesis of vicinal diamines (1). The process involves highly regio- and diastereoselective addition of 2-azaallyl anions (4) to N-tert-butanesulfinylimines (5) to produce vicinal diamines (1).