13669-70-0

Basic information

• Product Name: 3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene
• Synonyms: NEFOPAM;3-methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene;3,4,5,6-tetrahydro-5-methyl-1-phenyl-1h-2,5-benzoxazocine;3,4,5,6-tetrahydro-5-methyl-1-phenyl-1h-5-benzoxazocine;fenazoxine;Nefopam HCL CP2000;Nefopanhydrochloride;NEFOPAMI HCL
• CAS NO: 13669-70-0
• Molecular Formula: C₁₇H₁₉NO
• Molecular Weight: 253.34
• EINECS: 237-148-2
• Product Categories: ACTIVE PHARMACEUTICAL INGREDIENTS
• Mol File: 13669-70-0.mol

Chemical Properties

• Boiling Point: 396.54°C (rough estimate)
• Flash Point: 109 °C
• Appearance: /
• Density: 1.0078 (rough estimate)
• Vapor Pressure: 1.18E-05mmHg at 25°C
• Refractive Index: 1.5400 (estimate)
• Storage Temp.: 2-8°C
• PKA: 9.16±0.70(Predicted)
• CAS DataBase Reference: 3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene(13669-70-0)
• EPA Substance Registry System: 3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene(13669-70-0)

Safety Data

• Hazardous Substances Data: 13669-70-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene is used as an analgesic agent for the treatment of pain. Its non-opioid and non-steroidal nature makes it a valuable alternative to traditional pain medications, offering a different mechanism of action and potentially fewer side effects.
Used in Central Nervous System:
In the central nervous system, 3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene acts as a centrally acting analgesic, providing relief from pain by targeting the central nervous system rather than the site of pain itself. This makes it particularly useful for managing moderate to severe pain.
Brand Name:
Acupan (3M Pharmaceuticals) is a brand name under which 3-Methyl-7-phenyl-6-oxa-3-azabicyclo[6.4.0]dodeca-8,10,12-triene is marketed. This brand is associated with the pharmaceutical company 3M, which is known for its diverse range of products and innovations in various industries, including healthcare.

Originator

Ajan,Kettelhack Riker,W. Germany,1976

Manufacturing Process

The starting material is prepared by reacting 2-benzoylbenzoic acid with thionyl chloride and then with 2-methylaminoethanol. 20.0 grams (0.07 mol) of N-(2-hydroxyethyl)-N-methyl-o-benzoylbenzamide is suspended in 100 ml tetrahydrofuran and then slowly added in small portions to a solution of 5.5 grams (0.14 mol) of lithium aluminum hydride in 150 ml tetrahydrofuran with cooling and stirring. The mixture is then refluxed for 18 hours, cooled and then to it is successively added 5.5 ml water, 5.5 ml of 3.75 N sodium hydroxide and 16 ml water. After removal of precipitated salts by filtration, the solution remaining is concentrated under reduced pressure and the residue dried to yield 19.5 grams of crude product. Yield after conversion to the hydrochloride salt and recrystallization is 17.0 grams (89%), MP 128° to 133°C.5-methyl-1-phenyl-1,3,4,6-tetrahydro-5H-benz[f] -2,5-oxazocine is prepared as follows. 3.0 grams (0.011 mol) of 2-([N-(2-hydroxyethyl)-Nmethyl]amino)methylbenzhydrol, prepared as described above, 3.0 grams ptoluenesulfonic acid and 15 ml benzene are heated together with stirring until all the benzene is distilled off. The residual oil is heated to 105°C and held at this temperature for 1 hour, then cooled and dissolved in 30 ml water. This aqueous solution is then basified to pH 10.0 with 12 N sodium hydroxide, extracted with ether, and the extracts washed with water, dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The 2.26 grams (81%) oil remaining is converted to the hydrochloride salt, MP 238° to 242°C.

Therapeutic Function

Muscle relaxant, Antidepressant

InChI:InChI=1/C17H19NO/c1-18-11-12-19-17(14-7-3-2-4-8-14)16-10-6-5-9-15(16)13-18/h2-10,17H,11-13H2,1H3

Upstream product

• 84940-28-3 1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocine-5-carbonitrile 
• 17494-19-8 2,3-dihydro-9b-phenyloxazolo<2,3-a>isoindol-5(9bH)-one 
• 18409-76-2 2-(1-phenyl-2,3-dihydro-1H-isoindol-2-yl)ethanol 
• 23327-57-3 nefopam hydrochloride 
• 85-52-9 2-Benzoylbenzoic acid 
• 22103-85-1 2-benzoylbenzoyl chloride 
• 24833-47-4 2-benzoyl-N-(2-hydroxyethyl)-N-methylbenzamide 
• 60725-36-2 2-[{2-[hydroxyl(phenyl)methyl]benzyl}(methyl)amino]ethanol 

Downstream Products

• 865-50-9 iodomethane-d3 
• 129356-74-7 Nefopam trideuteriomethioiodide 
• 129356-74-7 Nefopam trideuteriomethioiodide 
• 66091-32-5 (1R,5S)/(1S,5R)-nefopam N-oxide 
• 66091-32-5 (1R,5R)/(1S,5S)-nefopam N-oxide 
• 129356-73-6 (+/-)-nefopam methiodide 
• 91463-82-0 (R)-5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine 
• 119-61-9 benzophenone 
• 13831-42-0 2-[(2-benzylbenzyl)(methyl)amino]ethanol 
• 60725-36-2 2-[{2-[hydroxyl(phenyl)methyl]benzyl}(methyl)amino]ethanol 
• 23327-57-3 nefopam hydrochloride 

Relevant articles and documents

MALODOR COUNTERACTING COMPOSITION AND AGENT AND THE USE THEREOF

The present invention relates to a malodor counteracting composition. In particular the invention relates to a malodor counteracting composition comprising nefopam, or a polymorph, a hydrate or a solvate thereof. The invention also relates to the use of said composition and attenuator or suppressor, for attenuating or suppressing malodors, in particular earthy, musty and/or moldy malodors.

Old is Gold? Nefopam Hydrochloride, a Non-opioid and Non-steroidal Analgesic Drug and Its Practical One-Pot Synthesis in a Single Solvent for Large-Scale Production

Nefopam hydrochloride is extensively used in most of the European countries until today as an analgesic because of its non-opiate (non-narcotic) and non-steroidal action with fewer side effects compared with opioid and other analgesics, which cause more troublesome side effects. A multikilogram synthesis of nefopam hydrochloride has been achieved in one pot using a single solvent (toluene). A ≥99.9% purity of the active pharmaceutical ingredient (API) was achieved in excellent overall yield (≥79%). The one-pot, five-step synthetic process involves formation of an acid chloride (3) from benzoylbenzoic acid (2) followed by amidation (4), reduction (5), cyclization (6), and formation of the hydrochloride salt (1). The major advantages include (i) use of a single solvent, (ii) >90% conversion in each step, (iii) a cost-effective and operationally friendly process, (iv) averting the formation of genotoxic impurities, and (v) improved overall yield (≥79%) provided by the one-pot operation. For the first time, we report the characterization data of API 1, intermediates 3, 4, and 5, and also a possible impurity (5a).

A PROCESS FOR THE RESOLUTION OF NEFOPAM

A process for increasing the optical purity of a mixture of enantiomers of nefopam uses a substantially single enantiomer of a O,O-diaroyltartaric acid as a resolving agent, via a bisnefopam salt of the acid. This salt is new.

Synthesis of Some 2,5-Benzoxazocine and 2,6-Benzoxazonine Derivatives from ω-(Dihydroisoindol-2-yl)alkanol Precursors by Means of Cyanogen Bromide

Reaction of cyanogen bromide with 2-(1-phenyl-2,3-dihydro-1H-isoindol-2-yl)ethanol (5a) gave 1-phenyl 3,4,5,6-tetrahydro-1H-2,5-benzoxazocine-5-carbonitrile (6a) in a low to moderate yield..Similarly, 3-(1-phenyl-2,3-dihydro-1H-isoindol-2-yl)propan-1-ol (5c) gave 1-phenyl-1,3,4,5,6,7-hexahydro-2,6-benzoxazonine-6-carbonitrile (6c).The analogous 1-(4-methoxyphenyl) derivatives of both medium ring systems were also prepared, and some mechanistic aspects of the results are discussed.Conversion of (6a) into the analgesic, Nefopam, is described.