- OLIGOMER-ARYLOXY-SUBSTITUTED PROPANAMINE CONJUGATES
-
The invention relates to (among other things) oligomer- aryloxy-substituted propanamine conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over un-conjugated aryloxy-substituted propanamine compounds.
- -
-
Paragraph 0256; 0260
(2016/11/17)
-
- Chemoenzymatic synthesis of (S)-duloxetine using carbonyl reductase from Rhodosporidium toruloides
-
A chemoenzymatic strategy was developed for (S)-duloxetine production employing carbonyl reductases from newly isolated Rhodosporidium toruloides into the enantiodetermining step. Amongst the ten most permissive enzymes identified, cloned, and overexpressed in Escherichia coli, RtSCR9 exhibited excellent activity and enantioselectivity. Using co-expressed E. coli harboring both RtSCR9 and glucose dehydrogenase, (S)-3-(dimethylamino)-1-(2-thienyl)-1-propanol 3a was fabricated with so far the highest substrate loading (1000 mM) in a space-time yield per gram of biomass (DCW) of 22.9 mmol L-1 h-1 g DCW-1 at a 200-g scale. The subsequent synthetic steps from RtSCR9-catalyzed (S)-3a were further performed, affording (S)-duloxetine with 60.2% overall yield from 2-acethylthiophene in >98.5% ee.
- Chen, Xiang,Liu, Zhi-Qiang,Lin, Chao-Ping,Zheng, Yu-Guo
-
supporting information
p. 82 - 89
(2016/02/23)
-
- Total synthesis of fluoxetine and duloxetine through an in situ imine formation/borylation/transimination and reduction approach
-
We report efficient, catalytic, asymmetric total syntheses of both (R)-fluoxetine and (S)-duloxetine from α,β-unsaturated aldehydes conducting five sequential one-pot steps (imine formation/copper mediated β-borylation/transimination/reduction/oxidation) followed by the specific ether group formation which deliver the desired products (R)-fluoxetine in 45% yield (96% ee) and (S)-duloxetine in 47% yield (94% ee). This journal is the Partner Organisations 2014.
- Calow, Adam D. J.,Fernandez, Elena,Whiting, Andrew
-
p. 6121 - 6127
(2014/08/05)
-
- METHYLHYDROXYLAMINOPROPANOL DERIVATIVE AND ITS USE AS INTERMEDIATE FOR PREPARATION OF 3-METHYLAMINO-1-(2-THIENYL)PROPAN-1-OL
-
The present invention provides a methylhydroxylaminopropanol derivative and the methylhydroxylaminopropanol derivative of the present invention is used as an intermediate for preparation of 3-methylamino-1-(2-thienyl)propan-1-ol, which is an intermediate for preparation of (+)-(S)—N-methyl-3-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine oxalate. The present invention also provides a process for preparing 3-methylamino-1-(2-thienyl)propan-1-ol with higher yield and lower cost, wherein the methylhydroxylaminopropanol derivative is used as an intermediate.
- -
-
Page/Page column 3-4
(2009/05/28)
-
- 5-Phenylthio-1,3-oxazinan-4-ones via hetero Diels-Alder reactions: synthesis of (R)- and (S)-Duloxetines and Fluoxetines
-
The synthesis of 5-phenylthio-1,3-oxazinan-4-ones, through a hetero Diels-Alder strategy, is described. The cycloadducts thus prepared have been shown to be useful intermediates for the synthesis of 1,3-aminoalcohols, valuable intermediates in the preparation of biologically significant molecules, e.g., optically active Duloxetines and Fluoxetines. In the course of this elaboration a novel microwave assisted desulfurization reaction is reported.
- Panunzio, Mauro,Tamanini, Emiliano,Bandini, Elisa,Campana, Eileen,D'Aurizio, Antonio,Vicennati, Paola
-
p. 12270 - 12280
(2007/10/03)
-
- METHODS FOR THE PRODUCTION OF 3-METHYLAMINO-1-(THIENE-2-YL)-PROPANE-1-OL
-
The invention relates to enzymatic and non-enzymatic methods for the production of 3-methylamino-1-(thiene-2-yl)-propane-1-ol; in addition to enzymes for carrying out said method; nucleic acid sequences coding for said enzymes, expression cassettes containing them, vectors and recombinant hosts.
- -
-
Page/Page column 33
(2008/06/13)
-
- PROCESS FOR PRODUCING N-MONOALKYL-3-HYDROXY-3-(2-THIENYL)PROPANAMINE AND INTERMEDIATE
-
The present invention provides a process for producing an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine represented by General Formula (2): wherein R is C1-4 alkyl, comprising the step of reducing (Z)-N-monoalkyl-3-oxo-3-(2-thienyl)propenamine represented by General Formula (1): wherein R is as defined above. According to the present invention, an N-monoalkyl-3-hydroxy-3-(2-thienyl)propanamine which is for use as an intermediate for various pharmaceuticals can be produced in an industrially inexpensive and easy manner.
- -
-
Page/Page column 6; 7
(2008/06/13)
-
- PROPANOLAMINE DERIVATIVES, PROCESS FOR PREPARATION OF 3-N-METHYLAMINO-1-(2-THIENYL)-1-PROPANOLS AND PROCESS FOR PREPARATION OF PROPANOLAMINE DERIVATIVES
-
The present invention provides means for preparing a racemate or an optically active substance (S- or R-isomer) of 3-N-methylamino-1-(2-thienyl)-1-propanol represented by the following general formula (I): wherein R1 represents any of a hydrogen atom, a C1-8 acyl group, a substituted or substituted C1-8 alkyloxycarbonyl group and a substituted or substituted phenyloxycarbonyl group and R2 represents any of a hydrogen atom, a C1-8 alkyl group, a substituted or substituted benzyl group, a C1-8 acyl group, a substituted or substituted C1-8 alkyloxycarbonyl group and a substituted or substituted phenyloxycarbonyl group, with the exception that R1 is a hydrogen atom and R2 is a methyl group or a hydrogen atom, in a simple manner at low cost and in high yield.
- -
-
Page/Page column 31
(2010/02/10)
-
- Practical synthesis of enantiopure γ-amino alcohols by rhodium-catalyzed asymmetric hydrogenation of β-secondary-amino ketones
-
(Chemical Equation Presented) Another way to antidepressants: A series of β-secondary-amino ketone hydrochlorides (e.g. 1) were hydrogenated with remarkably high enantioselectivities by using a Rh complex containing P-chiral bisphospholane 2. These results establish a short and practical means for the synthesis of enantiopure N-monosubstituted γ-amino alcohols (e.g. 3), which are key intermediates in the synthesis of important antidepressants. (nbd = norbornadiene; TON = turnover number).
- Liu, Duan,Gao, Wenzhong,Wang, Chunjiang,Zhang, Xumu
-
p. 1687 - 1689
(2007/10/03)
-
- Process for the preparation of enantiomerically pure 1-substituted-3-aminoalcohols
-
Provided is a process for the preparation of enantiomerically pure 1-substituted-3-amino-alcohols, particularly of (S)-(-)- and (R)-(+)-3-N-methylamino-1-(2-thienyl)-1-propanol, by asymmetrically hydrogenating salts of a carboxylic acids with an aminoketone of the formula wherein R1 is selected from the group consisting of 2-thienyl, 2-furanyl and phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein R2 is C1-4-alkyl or phenyl, each optionally substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, and wherein the corresponding aminoalcohols are obtained by subsequent hydrolysis of their salts. Furthermore provided are salts of a carboxylic acid with said aminoketones and the aminoalcohols obtained by asymmetriacally hydrogenating said aminoketones, respectively.
- -
-
Page/Page column 5
(2010/02/13)
-
- PROCESS FOR THE PREPARATION OF N-MONOSUBSTITUTED β-AMINO ALCOHOLS
-
The invention relates to a process for the synthesis of N-monosubstituted β-amino alcohols of formula (I) and/or an addition salt of a proton acid, wherein R1 and R2 independently represent alkyl, cycloalkyl, aryl or aralkyl, each being optionally further substituted with alkyl, alkoxy and/or halogen via direct preparation of N-monosubstituted β-amino ketones of formula and its addition salts of proton acids, wherein R1and R2 are as defined above.
- -
-
-
- PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE 3-N-METHYLAMINO-1-(2-THIENYL)-1-PROPANOL
-
Enantiomerically enriched (S)-(-)-3-N-methylamino-l-(2-thienyl)-1-propanol or (R)-(+)-3-N-methylamino-l-(2-thienyl)-l-propanol of the formulae, or mirror image are prepared by i) treating an enantiomeric mixture of the amines Ia and Ib with (-)-2,3:4,6-di-O-isopropylidene-2-keto-L-gulonic acid or (+)-2,3:4,6-di-O-isopropylidene-2-keto-D-gulonic acid of the formulae (IIa) or mirror image ii) crystallizing the obtained diastereomerically enriched salts from the reaction mixture obtained in step i), iii) optionally recrystallizing said diastereomerically enriched salts IIIa or IVb, and iv) treating the diastereomerically enriched salts IIIa or IVb obtained in step ii) or step iii) with a base to liberate the enantiomerically enriched amines Ia or Ib.
- -
-
-
- 3-METHYLAMINO-1-(2-THIENYL)-1-PROPANONE, PRODUCTION AND USE THEREOF
-
The invention relates to the production of 3-methylamino-1-(2-thienyl)-1-propanone and the use thereof for producing the pharmaceutical (+)-(S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine oxalate (trade name Duloxetine?).
- -
-
Page/Page column 4
(2008/06/13)
-