The present invention relates to a process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol.

The present invention relates to a process for the preparation of (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol.

The invention provides a method for synthesizing a compound of formula

##STR00001##

wherein each R independently represents an optionally substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, cyano, sulfo or sulfhydryl group, in ortho, meta or para position to the cycloalkylamine moiety; R.sup.1 and R.sup.2 each independently represents a hydrogen atom, a lower alkyl group or a cycloalkyl group; R.sup.3 represents a hydrogen group, substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy group; Y represents an oxygen atom, a sulfur atom, a NH group, a NR.sup.4 group or a CH.sub.2 group; R.sup.4 represents a hydrogen atom or an alkyl, aryl or a heteroaryl group; and n and m each independently represents an integer from 1 to 5; or a pharmaceutically acceptable salt thereof; or a precursor thereof; wherein the method comprises one or more of the following steps: (a) reacting a compound of formula (II)

##STR00002##

wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I) with an oxygenating agent, a first additive and a second additive in a solvent in a fluidic network or in a batch process under thermal and/or photochemical conditions to form a compound of formula (III):

##STR00003##

wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I), (b) reacting a compound of formula (III) with a nitrogen containing nucleophile in the presence of a third additive and/or a solvent in the fluidic network or in a batch process under thermal conditions to form a compound of formula (IV):

##STR00004##

wherein R, R.sub.1, R.sub.2, R.sub.3, Y, n and m are as defined above in relation to the compound of formula (I); and/or (c) reacting a compound of formula (IV) in a fluidic network or in a batch process, optionally in the presence of a fourth additive, under thermal conditions to form a compound of formula (I); wherein one or more of steps (a), (b) and/or (c) is carried out in a fluidic network that comprises micro- and/or meso-channels having an internal dimension of from 100 m to 2000 m.

The invention provides a method for synthesizing a compound of formula

##STR00001##

wherein each R independently represents an optionally substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, cyano, sulfo or sulfhydryl group, in ortho, meta or para position to the cycloalkylamine moiety; R.sup.1 and R.sup.2 each independently represents a hydrogen atom, a lower alkyl group or a cycloalkyl group; R.sup.3 represents a hydrogen group, substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy group; Y represents an oxygen atom, a sulfur atom, a NH group, a NR.sup.4 group or a CH.sub.2 group; R.sup.4 represents a hydrogen atom or an alkyl, aryl or a heteroaryl group; and n and m each independently represents an integer from 1 to 5; or a pharmaceutically acceptable salt thereof; or a precursor thereof; wherein the method comprises one or more of the following steps: (a) reacting a compound of formula (II)

##STR00002##

wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I) with an oxygenating agent, a first additive and a second additive in a solvent in a fluidic network or in a batch process under thermal and/or photochemical conditions to form a compound of formula (III):

##STR00003##

wherein R, R.sup.3, Y, n and m are as defined above in relation to the compound of formula (I), (b) reacting a compound of formula (III) with a nitrogen containing nucleophile in the presence of a third additive and/or a solvent in the fluidic network or in a batch process under thermal conditions to form a compound of formula (IV):

##STR00004##

wherein R, R.sub.1, R.sub.2, R.sub.3, Y, n and m are as defined above in relation to the compound of formula (I); and/or (c) reacting a compound of formula (IV) in a fluidic network or in a batch process, optionally in the presence of a fourth additive, under thermal conditions to form a compound of formula (I); wherein one or more of steps (a), (b) and/or (c) is carried out in a fluidic network that comprises micro- and/or meso-channels having an internal dimension of from 100 m to 2000 m.

This disclosure relates to a method for treating a disease which can be alleviated by inhibiting PAICS activity. The method includes administering a therapeutically effective amount of spermine or a pharmaceutically acceptable salt or C.sub.1-C.sub.6 amide thereof to a patient in need thereof.

This disclosure relates to a method for treating a disease which can be alleviated by inhibiting PAICS activity. The method includes administering a therapeutically effective amount of spermine or a pharmaceutically acceptable salt or C.sub.1-C.sub.6 amide thereof to a patient in need thereof.

Provided are applications of spermine and derivatives thereof. On the basis of existing protein structure data and small molecule structure data, calculations and analysis are performed using software to screen and obtain compounds capable of effectively interfering with PAICS activity, reducing SAICAR synthesis, and ultimately reducing SAICAR accumulation, in order to achieve the goal of treating or reducing ADSL deficiency. A better effect in the treatment or improvement of ADSL deficiency is expected from the joint use of at least two of the described compounds.

Provided are applications of spermine and derivatives thereof. On the basis of existing protein structure data and small molecule structure data, calculations and analysis are performed using software to screen and obtain compounds capable of effectively interfering with PAICS activity, reducing SAICAR synthesis, and ultimately reducing SAICAR accumulation, in order to achieve the goal of treating or reducing ADSL deficiency. A better effect in the treatment or improvement of ADSL deficiency is expected from the joint use of at least two of the described compounds.

Provided are an intermetallic compound having high stability and high activity, and a catalyst using the same. A hydrogen storage/release material containing an intermetallic compound represented by formula (1): RTX . . . (1) wherein R represents a lanthanoid element, T represents a transition metal in period 4 or period 5 in the periodic table, and X represents Si, Al or Ge.

Provided are an intermetallic compound having high stability and high activity, and a catalyst using the same. A hydrogen storage/release material containing an intermetallic compound represented by formula (1): RTX . . . (1) wherein R represents a lanthanoid element, T represents a transition metal in period 4 or period 5 in the periodic table, and X represents Si, Al or Ge.