54-49-9 Usage
Chemical Properties
Colourless solid
Originator
Aramine,MSD, US,1952
Uses
Different sources of media describe the Uses of 54-49-9 differently. You can refer to the following data:
1. Metaraminol is a sympathomimetic amine of both direct and indirect action that has hemodynamic characteristics similar to norepinephrine. It has the ability to elevate both systolic
and diastolic blood pressure.
It is used in hypotensive shock for the purpose of elevating blood pressure, which can
result from spinal anesthesia, surgical complications, and head trauma.
2. Adrenergic.
3. Metaraminol is a direct and indirect non-specific adrenoceptor agonist. It
acts primarily via α1-receptors, causing vasoconstriction with subsequent
increase in arterial pressure and reflex bradycardia. It is administered via i.v.
bolus injection at a dose of 0.5–2 mg, titrated to effect.
Definition
ChEBI: A member of the class of phenylethanolamines that is 2-amino-1-phenylethanol substituted by a methyl group at position 2 and a phenolic hydroxy group at position 1. A sympathomimetic agent , it is used in the treatment of hypotension.
Manufacturing Process
The hydrochloride of the m-hydroxyphenylpropanolamine may be prepared by
dissolving or suspending 90 parts of m-hydroxyphenylethyl ketone, O =
C(C6H4-OH)-C2H5, in about 400 parts of ether. Hydrogen chloride is slowly
bubbled through the solution or suspension while agitating it and 61.8 g of
butyl nitrite is added during the course of 60 to 90 minutes. During the
addition of the butyl nitrite the suspended m-hydroxyphenylethyl ketone
gradually dissolves. The mixture or solution is allowed to stand for at least an
hour, but preferably overnight. It is then repeatedly extracted with dilute alkali
until all alkali-soluble material is removed. The alkaline extract is slowly
acidified and the precipitate which forms is crude m-hydroxyphenyl-αoximinoethyl ketone. After recrystallization from water this melts at 138°C.
10.8 parts of the meta ketone is dissolved in about 125 parts of absolute
alcohol containing 5.6 parts of hydrogen chloride. The solution is agitated with
a catalyst such as the palladium catalyst above described in an atmsophere of hydrogen until no more hydrogen is absorbed. This requires from 60 to 90
minutes or more. When reduction is complete the catalyst is filtered off and
the filtrate evaporated to dryness by being placed in a desiccator at ordinary
temperature.
The residue is the hydrochloride of m-hydroxyphenyl-α-aminoethyl ketone.
This is purified by recrystallization from absolute alcohol. It is then dissolved
in 200 parts of water and agitated with a further quantity of the palladium
catalyst in an atmosphere of hydrogen until saturated. The product thus
recovered from the solution is the hydrochloride of m-hydroxyphenylpropanol
amine. After recrystallization from absolute alcohol this melts at 177°C. The
corresponding free base can be prepared from the hydrochloride by treatment
with ammonia, according to US Patent 1,995,709.
Metaraminol is often used in the form of the bitartrate.
Therapeutic Function
Hypertensive
General Description
Metaraminol is the N-desmethyl- -methylanalog of phenylephrine. It possesses a mixed mechanismof action, with its direct-acting effects mainly on 1-receptors. It is used parenterally as a vasopressor in thetreatment and prevention of the acute hypotensive stateoccurring with spinal anesthesia. It also has been used totreat severe hypotension brought on by other traumas thatinduce shock.
Clinical Use
#N/A
Synthesis
Metaraminol, L-1-(3-hydroxyphenyl)-2-aminopropan-1-ol (11.3.11), is synthesized in two ways. The first way is synthetic, and it is from 3-hydroxypropiophenone.
The hydroxyl group is protected by alkylation with benzyl chloride, giving 3-benzyloxypropiophenone (11.3.8). Upon reaction with butylnitrite, it undergoes nitrosation into
the isonitrosoketone (11.3.9), which by reduction using semisynthetic, consisting of fermentation of D-glucose in the presence
of 3-acetoxybenzaldehyde, which forms (-)-1-hydroxy-1-(3-hydroxyphenyl)-acetone
(11.3.12), the carbonyl group of which is reduced by hydrogen over a palladium catalyst
in the presence of ammonia, giving metaraminol (11.3.11) [62–65].
Drug interactions
Potentially hazardous interactions with other drugs
Adrenergic neurone blockers: hypotensive effect
antagonised.
Anaesthetics: risk of ventricular arrhythmias with
isoflurane - avoid.
Antibacterials: risk of hypertensive crisis with
linezolid and tedizolid - avoid for at least 2 weeks
after stopping linezolid and tedizolid.
Antidepressants: risk of hypertensive crisis with
MAOIs and moclobemide - avoid for at least 2
weeks after stopping MAOIs.
Dopaminergics: avoid with rasagiline and selegiline
Metabolism
Hepatically metabolised.
Check Digit Verification of cas no
The CAS Registry Mumber 54-49-9 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 4 respectively; the second part has 2 digits, 4 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 54-49:
(4*5)+(3*4)+(2*4)+(1*9)=49
49 % 10 = 9
So 54-49-9 is a valid CAS Registry Number.
InChI:InChI=1/C9H13NO2/c1-6(10)9(12)7-3-2-4-8(11)5-7/h2-6,9,11-12H,10H2,1H3/t6-,9-/m0/s1
54-49-9Relevant articles and documents
Synthesis of pharmaceutical drugs from cardanol derived from cashew nut shell liquid
Shi, Yiping,Kamer, Paul C. J.,Cole-Hamilton, David J.
supporting information, p. 1043 - 1053 (2019/03/12)
Cardanol from cashew nut shell liquid extracted from cashew nut shells was successfully converted into various useful pharmaceutical drugs, such as norfenefrine, rac-phenylephrine, etilefrine and fenoprofene. 3-Vinylphenol, the key intermediate for the synthesis of these drugs, was synthesised from cardanol by ethenolysis to 3-non-8-enylphenol followed by isomerising ethenolysis. The metathesis reaction worked very well using DCM, but the greener solvent, 2-methyl tetrahydrofuran, also gave very similar results. Hydroxyamination of 3-vinylphenol with an iron porphyrin catalyst afforded norfenefrine in over 70% yield. Methylation and ethylation of norfenefrine afforded rac-phenylephrine and etilefrine respectively. A sequence of C-O coupling, isomerising metathesis and selective methoxycarbonylation afforded fenoprofene in good yield. A comparison of the routes described in this paper with some standard literature syntheses of 3-vinylphenol and of the drug molecules shows significant environmental advantages in terms of precursors, yields, number of steps, conditions and the use of catalysts. The Atom Economy of our processes is generally similar or significantly superior to those of the literature processes mainly because the side products produced during synthesis of 3-vinylphenol (1-octeme, 1,4-cyclohexadiene and propene) are easily separable and of commercial value, especially as they are bio-derived. The E Factor for the production of 2-vinylphenol by our process is also very low compared with those of previously reported syntheses.
Enzymatic and Chemoenzymatic Three-Step Cascades for the Synthesis of Stereochemically Complementary Trisubstituted Tetrahydroisoquinolines
Erdmann, Vanessa,Lichman, Benjamin R.,Zhao, Jianxiong,Simon, Robert C.,Kroutil, Wolfgang,Ward, John M.,Hailes, Helen C.,Rother, D?rte
supporting information, p. 12503 - 12507 (2017/09/13)
Chemoenzymatic and enzymatic cascade reactions enable the synthesis of complex stereocomplementary 1,3,4-trisubstituted tetrahydroisoquinolines (THIQs) with three chiral centers in a step-efficient and selective manner without intermediate purification. The cascade employs inexpensive substrates (3-hydroxybenzaldehyde and pyruvate), and involves a carboligation step, a subsequent transamination, and finally a Pictet–Spengler reaction with a carbonyl cosubstrate. Appropriate selection of the carboligase and transaminase enzymes enabled the biocatalytic formation of (1R,2S)-metaraminol. Subsequent cyclization catalyzed either enzymatically by a norcoclaurine synthase or chemically by phosphate resulted in opposite stereoselectivities in the products at the C1 position, thus providing access to both orientations of the THIQ C1 substituent. This highlights the importance of selecting from both chemo- and biocatalysts for optimal results.
A heavy tartaric acid metaraminol synthetic method
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Paragraph 0048; 0049, (2017/02/09)
The invention discloses a synthesis method of metaraminol bitartrate, and in particular provides a method for synthesizing metaraminol bitartrate by using a chiral catalysis method. The synthesis method comprises the steps: catalyzing a chiral addition reaction of hydroxybenzaldehyde and nitroethane by using a chiral catalyst system consisting of cinchona alkaloid, copper acetate hydrate and less imidazole to obtain an addition product with a dominant required spatial configuration, and then reducing nitro by using hydrogen in the presence of Pd-C to obtain amine to obtain aramine, and salifying the aramine with L(+)-tartaric acid to obtain a final product metaraminol bitartrate. According to the synthesis method, an enzyme catalyst is prevented from being used, a raw material of the synthesis reaction is easily available, the chiral catalyst is easily purchased or prepared self, the synthesis steps are relatively less, the chiral control efficiency is higher, the enantioselectivity is high, the yield is good, the reaction operation is easily controlled, and is safe and reliable, and the foundation is laid for the later industrialized amplification production.