769092-24-2Relevant articles and documents
Continuous-Flow Synthesis of Tramadol from Cyclohexanone
Monos, Timothy M.,Jaworski, Jonathan N.,Stephens, John C.,Jamison, Timothy F.
supporting information, p. 1888 - 1893 (2020/11/24)
A multioperation, continuous-flow platform for the synthesis of tramadol, ranging from gram to decagram quantities, is described. The platform is segmented into two halves allowing for a single operator to modulate between preparation of the intermediate by Mannich addition or complete the fully concatenated synthesis. All purification operations are incorporated in-line for the Mannich reaction. 'Flash' reactivity between meta-methoxyphenyl magnesium bromide and the Mannich product was controlled with a static helical mixer and tested with a combination of flow and batch-based and factorial evaluations. These efforts culminated in a rapid production rate of tramadol (13.7 g°h -1) sustained over 56 reactor volumes. A comparison of process metrics including E-Factor, production rate, and space-time yield are used to contextualize the developed platform with respect to established engineering and synthetic methods for making tramadol.
Methods of synthesis of alicyclic 1,5,9-triketones. Reaction of transaminomethylation
Akimova,Soldatkina,Ivanenko, Zh. A.,Savchenko
, p. 720 - 728 (2017/07/07)
Alicyclic 1,5,9-triketones with various combination of 5-, 6-, 7-membereded cycles in the molecule were obtained by methods of diketone condensation, Michael reaction, and proceeding from Mannich mono- and bisbases and cycloalkanones. The latter method wa
Opioid Detection
-
Paragraph 0009; 0078, (2017/07/14)
An immunoassay method is described which detects O-desmethyltramadol only. This enables an assay of high sensitivity and specificity avoiding false positive results. The unique antibodies incorporated in the immunoassay method can be combined with antibodies which detect mitragynine to provide an assay which increases the possibility of detecting the commonly found drug combination of O-desmethyltramadol and mitragynine.
A novel method for biomimetic synthesis of Mannich bases
Guo, Yuan,An, Jing,Lu, Zhenhuan,Peng, Mengjiao
experimental part, p. 1561 - 1564 (2012/10/07)
Since the early studies of Mannich, Mannich reaction has become an important tool for the synthesis of new compounds. Mannich bases can be either directly employed or used as intermediates. In this work, the one-carbon unit transfer reaction of tetrahydrofolate coenzyme was initiated. 1,3-Dimethylimidazolidine as a new tetrahydrofolate coenzyme model at formaldehyde oxidation level was used to react with ketone having active hydrogen atoms and amine to give the corresponding Mannich base in good yield by a covert Mannich reaction. A novel method for biomimetic synthesis of various Mannich bases is provided. 1,3-Dimethylimidazolidine as a new tetrahydrofolate coenzyme model at formaldehyde oxidation level was used to react with ketone having active hydrogen atoms and amine to give the corresponding Mannich base in good yield by a covert Mannich reaction. A novel method for biomimetic synthesis of various Mannich bases is provided. Copyright
PROCESS FOR PREPARATION OF NORBORNENE DERIVATIVES
-
Page/Page column 26, (2012/05/04)
A method for producing a norbornene derivative, comprising: a first step of forming a Mannich base by reacting a carbonyl compound and an amine compound with each other in an acidic solvent, to thereby obtain a reaction liquid comprising the Mannich base in the acidic solvent, the acidic solvent comprising a formaldehyde derivative and 0.01 mol/L or more of an acid represented by the formula: HX (In the formula, X represents F or the like), the carbonyl compound being represented by any of the following general formulae (1) to (3): [in formulae (1) to (3), R1, R2, R3, R4, R5, and R6 each independently represent a hydrogen atom or the like, and n represents an integer of any of 0 to 4], the amine compound being represented by the following general formula (4): [in the formula (4), R7S each independently represent a linear chain saturated hydrocarbon group having 1 to 20 carbon atoms or the like, and X- represents F- or the like], the Mannich base being represented by any of the following general formulae (5) to (7): [R1, R2, R3, R4, R5, R6, and n in the formulae (5) to (7) have the same meanings as those of R1, R2, R3, R4, R5, R6, and n in the formulae (1) to (3), and R7 and X- in the formulae (5) to (7) have the same meanings as those of R7 and X- in the formula (4)] and a second step of reacting the Mannich base and a diene compound with each other by adding an organic solvent, a base in an amount of 1.0 to 20.0 equivalents to the acid, and the diene compound to the reaction liquid, and then heating the reaction liquid, to thereby form a norbornene derivative, the diene compound being represented by the following general formula (8): [in the formula (8), R8 represents a hydrogen atom or the like], the norbornene derivative being represented by any of the following general formulae (9) to (11): [R1, R2, R3, R4, R5, R6, and n in the formulae (9) to (11) have the same meanings as those of R1, R2, R3, R4, R5, R6, and n in the formulae (1) to (3), and R8 in the formulae (9) to (11) has the same meaning as that of R8 in the formula (8)].
SUBSTITUTED CYCLOHEXANOLS
-
Page/Page column 33, (2009/02/11)
Disclosed herein are substituted cyclohexanol opioid receptor modulators and/or neurotransmitter reuptake modulators of Formula I or Formula II, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
SULFONYLPYRAZOLE AND SULFONYLPYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS
-
Page/Page column 25-26, (2008/06/13)
This invention concerns sulfonylpyrazoline carboxamidine derivatives as antagonists of 5-HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1), wherein the symbols have the meanings given in the description.
Further exploration of 1-{2-[Bis-(4-fluorophenyl)methoxy]ethyl}piperazine (GBR 12909): Role of N-aromatic, N-heteroaromatic, and 3-oxygenated N-phenylpropyl substituents on affinity for the dopamine and serotonin transporter
Lewis, David,Zhang, Ying,Prisinzano, Thomas,Dersch, Christina M.,Rothman, Richard B.,Jacobson, Arthur E.,Rice, Kenner C.
, p. 1385 - 1389 (2007/10/03)
A series of N-aromatic, N-heteroaromatic, and oxygenated N-phenylpropyl derivatives of 1-(2-benzhydryloxyethyl)-piperazine and 1-{2-[bis-(4-fluorophenyl)methoxy]ethyl}piperazine, analogues of GBR 12909 (1a) and 12935 (1b), was synthesized and examined for their dopamine (DAT) and serotonin (SERT) transporter binding properties. One of these compounds, racemic 3-[4-(2-benzhydryloxyethyl)piperazin-1-yl]-1-(3-fluorophenyl)-propan-1-ol (33), had DAT affinity as good as, or better than, GBR 12909 and 12935, and was more selective for DAT over SERT than the GBR compounds. Both trans- (43) and cis- (47) (±)-2-(4-{2-[bis-(4-fluorophenyl)-methoxy]ethyl}piperazin-1- ylmethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol had relatively good SERT selectivity and, as well, showed high affinity for SERT.
Development of highly efficient resolutions of racemic tramadol using mandelic acid
Evans, Graham R.,Fernandez, Paloma Diaz,Henshilwood, James A.,Lloyd, Steve,Nicklin, Chris
, p. 729 - 737 (2013/09/06)
Two methods for the resolution of tramadol are described. One uses the active pharmaceutical ingredient (API), tramadol hydrochloride as input material. The other utilises the crude free base obtained from the Grignard reaction on tramadol Mannich base. B
Dimethyl-(3-aryl-but-3-enyl)-amine compounds as pharmaceutical active ingredients
-
, (2008/06/13)
Dimethyl-(3-aryl-but-3-enyl)-amine compounds, a method of preparing them, and the use of the compounds as pharmaceutical active ingredients are described.
