Fermion Oy

Orion Corporation

Orion Corporation, Fermion

Ilpo Laitinen

Mikko Kalervo Mäkelä

Oskari Karjalainen

Hannele Nikander

Mikko Mäkelä

Mikko Leskinen

The present disclosure relates to an improved process for the preparation of isochroman structured alpha2A adrenoceptor agonist, namely 2-(5-methoxyisochroman-1-yl)-4,5-dihydro-1H-imidazole of formula (I) and a pharmaceutically acceptable salts thereof, such as 2-(5-methoxyisochroman-1-yl)-4,5-dihydro-1H-imidazole hydrogensulfate of formula (Ia), and to a novel intermediate compound used in the process, namely N-(2-aminoethyl)-5-methoxyisochroman-1-carboxamide monohydrate of formula (V). Alpha2A agonists are useful in the treatment of anxiety, and for use as a sedative or analgesic agent, and other diseases where alpha2A agonism is desired.

Process for the preparation of 2-(5-methoxyisochroman-1-yl)-4,5-dihydro-1H-imidazole and the hydrogensulfate salt thereof

The present invention relates to an improved process for the preparation of carboxamide structured androgen receptor (AR) antagonists such as N&#x2014;((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (1A) and key intermediates thereof such as 2-chloro-4-(1H-pyrazol-3-yl)benzonitrile (V). AR antagonists are useful in the treatment of cancer, particularly prostate cancer and other diseases where AR antagonism is desired. 

Process for the preparation of androgen receptor antagonists and intermediates thereof

The invention discloses the preparation method of 7-ethyl-10-hydroxycamptothecin from 4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione and 1-(2-amino-5-hydroxyphenyl)-propan-1-one using higher reaction temperature and faster heating to that temperature.

Process for the manufacturing of 7-ethyl-10-hydroxy camptothecin

The present invention is directed to a novel method for the preparation of high purity irinotecan. This can be achieved by eliminating the excess of the other reagent, bipiperidinyl-1'-carbonyl chloride after it has reacted with 7-ethyl-10-hydroxy camptothecin and crystallizing the final product from a suitable solvent.

Preparation method

The present invention is related to a process for the preparation of [1,4']bipiperidinyl-1&#x2032;-carbonyl chloride or its hydrochloride using methylene chloride as a solvent in the reaction of 4-piperidinopiperidine with phosgene and the removing the reaction solvent by using an additional distillation solvent to raise the distillation temperature.

Process for producing [1,4'] bipiperidinyl-1&#x2032;-carbonyl chloride or hydrochloride thereof

Sertraline hydrochloride, (1Scis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphtalenaminehydrochloride, polymorph II is prepared by extracting or dissolving the sertraline base into ethyl acetate, adding isopropanol as a solvent, adding hydrogen chloride dissolved in ethyl acetate or in gaseous form, and finally isolating and drying sertraline hydrochloride polymorphic form II.

Process for preparing sertraline hydrochloride polymorphic form II

(1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (sertraline) may be prepared by hydrogenating of N-&lsqb;4-(3,4-dichlorophenyl)-3, 4-dihydro-1(2H)-naphthalenylidene&rsqb;methanamine in the presence of a dehalogenation inhibitor, e.g., triphenylphosphite or trimethylphosphite and a catalyst.

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Espoo, Finland

Ilpo Laitinen