Novartis Ag

Novartis Pharmaceuticals Corporation

Bin Hu

Nan Ji

Michael H Serrano-Wu

Mahavir Prashad

Michael John Girgis

Yugang Liu

Prasad Koteswara Kapa

Christopher Michael Adams

Paul Allen Sutton

Piotr Henryk Karpinski

Lili Feng

Liladhar Murlidhar Waykole

Bernhard Wietfeld

Toshio Kawanami

Erik Meredith

Rajeshri Ganesh Karki

Thomas J Blacklock

David Hook

Ulrich Meier

Chang Rao

Timothy Brian Hurley

Sven Erik Godtfredsen

Joel Slade

Denis Har

Olivier Lohse

Hong-Yong Kim

Florian Karl Kleinbeck

Xinglong Jiang

Jean-Paul Mutz

Jan Schlomach

Sibylle Mueller

Thomas Blacklock

Christina Cappaci-Daniel

The invention relates to polymorphic forms of the calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester. The calcium salt of N-(3-carboxyl-1-oxopropyl)-(4S)-(p-phenylphenylmethyl)-4-amino-(2R)-methyl butanoic acid ethyl ester is useful in the treatment of various conditions and disorders responsive to the inhibition of neutral endopeptidases.

Sacubitril calcium salts

An amorphous solid form of a compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and sodium cations is provided. This is compound is useful for the treatment of hypertension and/or heart failure.

Amorphous solid form of compounds containing S&#x2014;N-valeryl-N- {[2'-( 1 H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and sodium cations

An amorphous solid form of a compound comprising the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and sodium cations is provided. This compound is useful for the treatment of hypertension and/or heart failure.

Amorphous solid form of compounds containing S&#x2014;N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and sodium cations

A method for treatment of a cardiovascular or renal condition or disease with a specific combination, linked pro-drug or a compound of an angiotensin receptor antagonist and a NEPi.

Compounds containing S-N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl)-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations

A compound of an angiotensin receptor antagonist (ARB), a neutral endopeptidase inhibitor (NEPi) and one or more monovalent cations are useful for the treatment of hypertension and/or heart failure. ARB includes S&#x2014;N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine in the anion form, NEPi includes (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester in the anion form and cation includes monovalent cations such as Na. The compound includes trisodium [3-((1S,3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl)propionate-(S)-3&#x2032;-methyl-2&#x2032;-(pentanoyl{2&#x2033;-(tetrazol-5-ylate)biphenyl-4&#x2032;-ylmethyl}amino)butyrate] hemipentahydrate.

Compounds containing S-N-valeryl-N-{[2'-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine and (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester moieties and cations

Improved processes for preparing intermediates useful for preparing antibacterial N-[1-oxo-2-alkyl-3-(N-hydroxyformamido)-propyl}-(carbonylamino-aryl or -heteroaryl)-azacyclo4-7alkanes or thiazacyclo4-7alkanes, which have one or more of the following features: (1) make use of a particular &#x3b2;-lactam intermediate; (2) which make use of a particular resolving agents, enantiomerically pure substituted propionic acids, especially (R)-2-butyl-3-hydroxy-propionic acid; (3) which avoid the use of hydrogen peroxide; and (4) which facilitate selective debenzylation reducing production of waste by-products.

[object Object]

A process for preparing 5,6-diethyl-2,3-dihydro-1H-inden-2-amine and acid addition salts thereof from 2-aminoindan. The process comprises protecting the amino group of 2-aminoindan, acetylating the ring in the protected compound, reducing the acetyl group to ethyl to form a monoethyl derivative, acetylating the monoethyl derivative, reducing the acetyl group to form a diethyl derivative, deprotecting the latter by hydrolysis and recovering the product in free or salt form. The process does not use deleterious Grignard reagents or nitrites such as isoamyl nitrite, and provides high regioselectivity and high yield of 5,6-diethyl-2,3-dihydro-1H-inden-2-amine. In addition, the process uses acetyl halide as both a reactant and a solvent.

Process for preparing 5,6-diethyl-2,3-dihydro-1H-inden-2-amine

A process for preparing the d-threo isomer of methylphenidate hydrochloride comprising converting d,l-threo methylphenidate hydrochloride to the free base form in a first step, resolving the free base prepared in the first step with (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate to obtain the phosphate salt enriched with the d-threo isomer of methylphenidate in a second step, basifying the phosphate salt to obtain the free base form of the d-threo isomer of methylphenidate in a third step, converting the free base to the hydrochloride salt form of the d-threo isomer of methylphenidate in high optical purity in a fourth step, and recrystallizing the hydrochloride salt form to obtain the desired d-threo isomer in a higher optical purity. An alternative embodiment relates to the preparation of the d-threo isomer of methylphenidate hydrochloride utilizing the hydrochloride salt form of the racemic mixture of threo-methylphenidate directly.

Process for preparing the d-threo isomer of methylphenidate hydrochloride

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Green Brook, NJ, United States of America

Bin Hu