34911-55-2 Usage
Description
Bupropion, also known as Wellbutrin, is an aminoketone antidepressant that is structurally unrelated to tricyclics or tetracyclics. It functions as a dopamine uptake blocker and exhibits complex mechanisms of action, including the blockage of dopamine reuptake via the dopamine transporter (DAT) and noradrenergic antidepressant activity. Bupropion hydrochloride has a comparable clinical efficacy to amitriptyline but is not associated with orthostatic hypotension or other cardiovascular side-effects.
Uses
Used in Pharmaceutical Industry:
Bupropion is used as an antidepressant for treating major depressive disorders. It works by blocking the reuptake of dopamine, leading to an increase in the levels of dopamine in the brain, which contributes to its antidepressant effects.
Used in Sleep Disorder Treatment:
Bupropion is used as a treatment for sleep disorders associated with pain. Its mechanism of action helps alleviate pain and improve sleep quality in patients suffering from such conditions.
Used in Vasoconstriction:
Bupropion is used as a vasoconstrictor, functioning as a non-selective agonist of all adrenergic receptors. This application is particularly useful in medical procedures where constriction of blood vessels is required.
Used in Drug Interaction Studies:
Due to the presence of active metabolites, such as hydroxybupropion, threohydrobupropion, and erythrohydrobupropion, Bupropion is used in studying drug interactions, especially those involving cytochrome P450 2D6 (CYP2D6). Understanding these interactions is crucial for optimizing treatment regimens and minimizing potential adverse effects.
Originator
Burroughs Wellcome (United Kingdom)
Manufacturing Process
To ethyl magnesium bromide (2 L, 3 M) was added over 45 min with stirring
and cooling m-chlorobenzonitrile (688.0 g, 5 mole) in ether (2.5 L). The
resultant solution was heated under gentle reflux for 5 h. The reaction mixture
was hydrolyzed with cold dilute hydrochloric acid, the ether was distilled off,
and the aqueous solution was heated at 90°C for 1 h. The flask was then
cooled. The solid ketone that separated was washed with cold water and
recrystallized from methanol. The recrystallized m-chloropropiophenone,
melting point 39°-40°C, weighed 750.0 g.
In methylene chloride (3 L) was dissolved m-chloropropiophenone (698.0 g;
4.15 mole). The solution was stirred with charcoal (Darco) and magnesium
sulfate for 2 h and filtered. To it was added with stirring (662.0 g) of bromine
in methylene chloride (1 L). When the bromine color had faded completely,
the solvent was evaporated in vacuum and m-chloro-α-bromopropiophenone
was obtained as oil.
The m-chloro-α-bromopropiophenone was dissolved in acetonitrile (1300 ml).
To this, t-butylamine (733.0 g) in acetonitrile (1300 ml) was added while
keeping the temperature below 32°C. The reaction mixture was allowed to
stand over night. It was then partitioned between water (4200 ml) and ether
(2700 ml). The aqueous layer was extracted with a further portion of ether
(1300 ml). The combined ethereal layers were then washed with water (4200
ml) to which hydrochloric acid was added until the pH of the aqueous layer
was 9. The aqueous layer was separated and washed with ether (500 ml) and
then discarded. The combined ethereal layers were then stirred with ice
(560.0 g) and concentrated hydrochloric acid (324 ml). The ethereal layer was
separated and again washed with water (200 ml) and concentrated
hydrochloric acid (50 ml). These last two acid layers were combined and
concentrated in vacuum until crystals appeared. The solution was then chilled
to 5°C and filtered. The product was sucked dry, washed with acetone and
recrystallized from a mixture of isopropanol (3 L) and absolute ethanol (800
ml). The DL-m-chloro-α-t-butylaminopropiophenone hydrochloride so was
obtained, melting point 233°-234°C.
The DL-m-chloro-α-t-butylaminopropiophenone was obtained by treatment of
DL-m-chloro-α-t-butylaminopropiophenone hydrochloride with sodium
hydroxide.
Biological Functions
Bupropion (Wellbutrin) is a pharmacologically unique
antidepressant, since it is a weak inhibitor of both dopamine
and norepinephrine neuronal reuptake. However,
its actual antidepressant activity is not well understood.
Bupropion is generally well tolerated and does
not block muscarinic, histaminergic, or adrenergic receptors.
Unlike the SSRIs and venlafaxine, bupropion
does not cause sexual side effects. However, it can cause
CNS stimulation, including restlessness and insomnia.
High doses of bupropion, given as its original formulation,
were associated with a risk of seizures in 0.4% of
patients. However, this risk is lower with slow-release
bupropion (Wellbutrin SR). This formulation still requires
dosing twice a day, and bupropion is contraindicated
in patients with a history of seizures. Bupropion
inhibits the cytochrome P450 2D6 isoenzyme and may
elevate blood levels of drugs metabolized by this route.
Pharmacology
Bupropion is an α-aminoketone that is structurally related to amphetamines, and it exhibits
unique activity comparable to that of other antidepressants. It is believed that bupropion
restores the total amount of norepinephrine in the body. This compound is a poor reuptake
inhibitor of dopamine, and does not exhibit anticholinergic activity or inhibit MAO. Its
efficacy as an antidepressant is comparable to that of tricyclic antidepressants, and as a
serotonin uptake inhibitor it is comparable to fluoxetine.
Synthesis
The synthesis of bupropion, 1-3(-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-
1-propanone (7.3.5), begins with the reaction of 3-chlorobenzonitrile, with ethylmagnesium
bromide to give 3-chloropropiophenone (7.3.3). Brominating this with bromine gives
3-chloro-α-bromopropiophenone (7.3.4), which on reaction with tert-butylamine gives bupropion (7.3.5) [54–58].
Check Digit Verification of cas no
The CAS Registry Mumber 34911-55-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,4,9,1 and 1 respectively; the second part has 2 digits, 5 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 34911-55:
(7*3)+(6*4)+(5*9)+(4*1)+(3*1)+(2*5)+(1*5)=112
112 % 10 = 2
So 34911-55-2 is a valid CAS Registry Number.
InChI:InChI=1/C13H18ClNO/c1-9(15-13(2,3)4)12(16)10-6-5-7-11(14)8-10/h5-9,15H,1-4H3
34911-55-2Relevant articles and documents
Across-the-World Automated Optimization and Continuous-Flow Synthesis of Pharmaceutical Agents Operating Through a Cloud-Based Server
Fitzpatrick, Daniel E.,Maujean, Timothé,Evans, Amanda C.,Ley, Steven V.
supporting information, p. 15128 - 15132 (2018/10/31)
The power of the Cloud has been harnessed for pharmaceutical compound production with remote servers based in Tokyo, Japan being left to autonomously find optimal synthesis conditions for three active pharmaceutical ingredients (APIs) in laboratories in Cambridge, UK. A researcher located in Los Angeles, USA controlled the entire process via an internet connection. The constituent synthetic steps for Tramadol, Lidocaine, and Bupropion were thus optimized with minimal intervention from operators within hours, yielding conditions satisfying customizable evaluation functions for all examples.
1,3-Dibromo-5,5-dimethylhydantoin (DBH) mediated one-pot syntheses of α-bromo/amino ketones from alkenes in water
Xu, Senhan,Wu, Ping,Zhang, Wei
, p. 11389 - 11395 (2016/12/18)
α-Bromo ketones are versatile intermediates of high practical utility. Traditional approaches to these compounds are restricted to a relatively hazardous/complex reagent combination, a long reaction time, the use of non-environmentally friendly solvents, or a limited substrate scope. Herein, we describe the development of a new methodology for the preparation of α-bromo ketones from alkenes using 1,3-dibromo-5,5-dimethylhydantoin (DBH) as a bromine source and an oxidant simultaneously. This easy to carry out two-step one-pot protocol proceeds in water and provides high yield of a great variety of α-bromo ketones. Addition of an amine to the intermediate α-bromo ketone further enables the preparation of α-amino ketones in a one-pot sequence.
Hyphenating the curtius rearrangement with morita-baylis-hillman adducts: Synthesis of biologically active acyloins and vicinal aminoalcohols
Amarante, Giovanni W.,Cavallaro, Mayra,Coelho, Fernando
, p. 1568 - 1584 (2011/11/06)
Using Morita-Baylis-Hillman adducts as substrates, the Curtius rearrangement was performed in a sequence that allowed the synthesis of several hydroxy-ketones (acyloins) with great structural diversity and in good overall yields. These acyloins in turn were easily transformed into 1,2-anti aminoalcohols through a highly diastereoselective reductive amination step. The synthetic utility of these approaches was exemplified by performing the syntheses of (±)-bupropion, a drug used to treat the abstinence syndrome of smoker and (±)-spisulosine, a potent anti-tumoral compound originally isolated form a marine source.
