1012341-48-8Relevant articles and documents
Method for synthesizing AHU377 calcium salt
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Paragraph 0016; 0027; 0033; 0037; 0043, (2020/04/02)
The invention discloses a method for synthesizing an AHU377 calcium salt. The method comprises the following steps: reacting 4-bromo-D-phenylalanine with thionyl chloride, reacting obtained methyl 4-bromo-D-phenylalaninate hydrochloride with BOC acid anhydride, reacting the obtained reaction product with phenylmagnesium bromide to obtain N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methylester, reacting the N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methyl ester with sodium borohydride, reacting the obtained reaction product with ethyl 2-(triphenylphosphoranylidene)propionate to obtain ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoate, reacting the ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoatewith lithium hydroxide, performing catalytic hydrogenation, reacting the obtained catalytic hydrogenation product with thionyl chloride to obtain ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, and stirring and reacting the ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, calcium chloride and succinic anhydride to obtain the target product.The method has the advantages of simple steps, mild reaction conditions, high purity and high yield.
Preparation method of LCZ-696 key intermediate
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Paragraph 0031; 0032; 0033, (2017/08/29)
The invention relates to a preparation method of an LCZ-696 key intermediate. The preparation method of the LCZ-696 key intermediate provided by the invention comprises the steps that a compound I is added into ethyl alcohol; lithium hydroxide and pure water are added; heat insulation reaction is performed for 1 to 2h at 78 to 82 DEG C; temperature reduction is performed; active carbon is added for decolorization; then, the temperature is raised to 80 to 85 DEG C; heat insulation backflow is performed for 1 to 3h; filtering is performed; filtering liquid is collected; a citric acid monohydrate or citric acid water solution is dripped; reaction stops; heat insulation backflow is performed for 1 to 2h at 80 to 85 DEG C; temperature reduction, stirring, crystallization, filtering and drying are performed to obtain a pure white solid compound II; a catalyst and a ligand are added; hydrogen gas is introduced; the pressure is maintained to be 1.5 to 3.5Mpa; reaction is performed for 20 to 40h at 70 to 80 DEG C to obtain reaction liquid of a compound III. The preparation method has the advantages that the yield of the compound II is improved to 8 to 12 percent from that of the prior art; the refining step is omitted; the operation difficulty is lowered; the industrial production is facilitated; meanwhile, the conversion rate of the compound II is improved by 30 to 40 percent through being compared with that of palladium-carbon hydrogenation, so that the cost of the compound III is greatly reduced; in addition, the optical isomers of the product are reduced; the reaction conversion rate is greatly improved.
PROCESS FOR THE PREPARATION OF INTERMEDIATES FOR THE MANUFACTURE OF NEP INHIBITORS
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Paragraph 0147, (2013/06/28)
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.
