Trazodone Hydrochloride

Synthesis of Trazodone Hydrochloride

The Trazodone Hydrochloride drug molecule (Compound T), was prepared using the process
described in Scheme 1, which involves simple condensation of 1-(3-chlorophenyl)-4-(3-
chloropropyl) piperazine and 1, 2, 4-triazolo [4, 3-a] pyridine-3- (2H)-one intermediates [8].
In first part of the process bis-(2-chloroethylamine) hydrochloride (Compound P) is prepared
by chlorination of diethanolamine with thionyl chloride in xylene, which is then condensed
with 3-chloro aniline to get 1-(3-chlorophenyl)-piperazine hydrochloride intermediate
(Compound Q). This is reacted with 3-bromo-3-chloropropane in alkaline aqueous acetone
(50 %) gave various 1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine intermediate
(Compound R). In second part of the process, 1-(3-chlorophenyl)-4-(3-chloropropyl)
piperazine is condensed with sodium salt of 1, 2, 4-triazolo [4, 3-a] pyridine-3- (2H)-one
(Compound S) prepared in a single step process by reaction of 2-chloropyridine and
semicarbazide hydrochloride in 2-ethoxyethanol afforded lead compound (Compound T),
isolated as hydrochloride salt. The yields of 1-(3-chlorophenyl)-piperazine hydrochloride (Q),
1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine (R) and of Trazodone Hydrochloride (T)
reported in the literature and observed in the lab are 84-85%, 72-73%, 84-85% respectively.
The intermediate 1, 2, 4-triazolo [4, 3-a] pyridine-3- (2H)-one (S) is obtained in >90 % yield
and in desired purity. But the process involves long reaction hours (>12) and elevated
temperature (145-150 0C).

http://jocpr.com/vol2-iss5-2010/JCPR-2010-2-5-506-517.pdf

IR

3000 (aromatic C-H stretching),
2954 (aliphatic C-H stretching),
1704 (C=O stretching),
1650 (C=N stretching),
1600 (aromaticC=C stretching),
1350 (C-N stretching),
750 (C-Cl stretching)



NMR
ð 2.16-2.12 ppm (t, 2H, -CH2),
2.64-2.60 (t, 2H, -N CH2),
2.73 (s,4H, -CH2-N-CH2),
3.09 (s, 4H, CH2-N-CH2),
4.12-4.07 (t, 2H,-CH2-N),
6.51-6.46 (m,1H, -ArH),
7.02-6.93 (m, 2H,-ArH),
7.09-7.08 (d, 2H, -ArH),
7.26-7.17 (m, 1H, -ArH),
7.34-7.31 (d, 1H, -ArH),
7.76-7.74 (d, 1H, -ArH)

SEE........http://pubs.rsc.org/en/content/articlelanding/2010/ay/c0ay00290a/unauth#!divAbstract

A robust method for in vitro metabolite generation and facile sample preparation on analyticalHPLC was established for rapid structure determination of microgram-level drug metabolites by using high-field NMR equipped with a cryoprobe. A single 1–5 mL incubation of drug candidate (10–30 μM) in microsomes, hepatocytes, or recombinant drug-metabolising enzymes, typicallycytochrome P450s and UDP-glucuronosyltransferases, was used for metabolite formation. Following precipitation of proteins and solvent removal, metabolite mixtures were chromatographed with 5–10 injections onto an HPLC-MS system. Metabolites were collected into a 96-well plate, dried, and reconstituted in deuterated NMR solvents. NMR spectra of isolated metabolites were acquired on a 500 MHz spectrometer equipped with a 5 mm cryogenic probe. The methodology has been successfully employed as an extension of HPLC-MS/MS-based metabolite identification and applied frequently to 0.5–10 μg quantities of metabolite. Most structure determinations were achieved rapidly by 1D ¹H NMR with satisfactory signal-to-noise ratios, whereas some required 2D NMR data analysis. This report describes the method development and metabolite structure determination using the model compoundtrazodone. In addition to trazodone, a large number of examples from our laboratories have proven that the microgram-level NMR method avoids time-consuming preparative-scalemetabolite generation and purification and circumvents technical complications associated with online LC-NMR. Most importantly, the turnaround time of metabolite structure determination for metabolically unstable compounds using the present methodology is more in sync with the cycle time during which medicinal chemists modify metabolic softspots while performing other iterative lead optimisation activities, demonstrating a real impact on the drug-discovery process.

NMR PREDICTIONS

H-NMR spectral analysis

CAS NO. 25332-39-2, Trazodone hydrochloride H-NMR spectral analysis

C-NMR spectral analysis

CAS NO. 25332-39-2, Trazodone hydrochloride C-NMR spectral analysis

//////////////////////////////



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http://newdrugapprovals.org/

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO

LATUR, MAHARASHTRA, INDIA

http://en.wikipedia.org/wiki/Latur

Latur लातूर Lattalur, Ratnapur
City
Latur Location in Maharashtra, India
Coordinates: 18.40°N 76.56°ECoordinates: 18.40°N 76.56°E
Country	India
State	Maharashtra
Region	Aurangabad Division
District	Latur
Settled	Possibly 7th century AD
Government
• Body	Latur Municipal Corporation
• Mayor	Akhtar Shaikh
Area[1]
• Total	117.78 km2(45.48 sq mi)
Area rank	89
Elevation	515 m (1,690 ft)
Population (2011)
• Total	382,754
• Rank	89th
• Density	3,200/km2(8,400/sq mi)
Demonym	Laturkar
Languages
• Official	Marathi
Time zone	IST (UTC+5:30)
PIN	413 512 413 531
Telephone code	91-2382
Vehicle registration	MH-24
Sex ratio	923.54 ♀/1000 ♂
Literacy	89.67
Distance from Mumbai	497 kilometres (309 mi) E (land)
Distance fromHyderabad	337 kilometres (209 mi) NW (land)
Distance fromAurangabad, Maharashtra	294 kilometres (183 mi) SE (land)
Climate	BSh (Köppen)
Precipitation	666 millimetres (26.2 in)
Avg. summer temperature	41 °C (106 °F)
Avg. winter temperature	13 °C (55 °F)
http://www.citypopulation.de/world/Agglomerations.html

his Is The Famous 'Ganj-Golai' As The Central Place Of The Latur City. There Are 16 Roads Connecting To This Place And Seperate Markets i.e. Jewellers ...




लातूर जिल्हयातील चित्र संग्रह

1. Colleges and Universities
   View 2+ more

   

   Rajarshi Shahu College...

    

   

   Government Medical College...

    

   

   M. S. Bidve Engineering College...

    

   

   Mahatma Basweshwar College L...

    

   

   Dayanand Pharmacy College L...

LATUR AIRPORT

LATUR AIRPORT













2012 Navratri Mahotsav in Latur





SOS Children's Village Latur











Latur, India: Carnival Resort









Ausa Near Latur







Chakur near Latur



Vilasrao Deshmukh's ancestral home at Babhalgaon village in Latur. Machindra Amle

















UDGIR: Udgir is one of the most important towns of Latur district. Udgir has a great historical significance. It has witnessed the war between the Marathas ...







The city of Latur is located in India's welathiest state, Maharashtra. Together with many of the surrounding villages, Latur was all but destroyed in the 

Raspberry ketone .Your aunt will teach you nmr

Raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; RK), one of the major aromatic compounds of raspberry, is widely used in perfumery, in cosmetics, and as a flavoring agent in foodstuffs








 amcrasto@gmail.com


RK: colorless needles crystal; m.p. 82–84 °C; 


ESI/MS m/z: 163 [M-H]+; 



1H-NMR (CDCl3, 500 MHz) δ: 2.14 (3H, s, H-1), 2.74 (2H, t, J = 7.5 Hz, H-3), 2.82 (2H, t, J = 7.5 Hz, H-4), 6.75 (2H, d, J = 8.5 Hz, H-3′,5′), 7.04 (2H, d, J = 8.5 Hz, H-2′,6′); 

 amcrasto@gmail.com







13C-NMR (CDCl3, 125 MHz) δ: 209.0 (C-2, C=O), 154.0 (C-4′), 132.8 (C-1′), 129.4 (C-2′, 6′), 115.3 (C-3′, 5′), 45.4 (C-3), 30.1 (C-4), 28.9 (C-1).


 - See more at: http://www.mdpi.com/1422-0067/12/8/4819/htm

Nechepurenk, V; Polovinka, NP; Sal¢nikova, OI; Pokrovskii, LM; Komarova, NI; Salakhutdinov, NF; Nechepurenk, SB. Compounds of the ehtylacetate extract of Hedysarum theinum roots. Chem. Nat. Compd 2007, 43, 5–9






NMR PREDICTIONS

H-NMR spectral analysis

CAS NO. 5471-51-2, 4-(4-Hydroxyphenyl)-2-butanone H-NMR spectral analysis

C-NMR spectral analysis

CAS NO. 5471-51-2, 4-(4-Hydroxyphenyl)-2-butanone C-NMR spectral analysis

More 4-(4-Hydroxyphenyl)-2-butanone NMR spectra of reference

//////////////////////////  amcrasto@gmail.com

http://newdrugapprovals.org/

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO

Simple tips to predict NMR..learn from your aunt

Nuclear Magnetic Resonance

(1) Predicting molecular structure :

An N.M.R. spectrum can reveal all the information needed to draw a structural formula for a molecule.

Example - the 1H-NMR spectrum of styrene oxide

The x-axis of the spectrum uses δ values for protons measured in ppm (parts per million), which indicate how different the resonances of the protons are to each other. This is called the chemical shift of the proton.  The lower the δ value the more saturated the environment of the proton, e.g. CH3CH2CH2CH3protons at about δ=1-2 ppm. The higher the d value the more unsaturated the environment of the proton, e.g. C6H6 protons at about δ=7 ppm.

The δ values for different types of protons are given on the datasheet and reproduced here :

type of proton :	chemical shift, δ
R-CH3	0.7 - 1.6
R-CH2-R	1.2 - 1.4
R3CH	1.6 - 2.0
	2.0 - 2.9
	2.3 - 2.7
-O-CH3    -O-CH2-R	3.3 - 4.3
R-OH	3.5 - 5.5 (but very variable)
	6.5 - 7.0
	7.1 - 7.7
	9.5 - 10.0
	11.0 - 11.7

The different types of protons in a molecule all give rise to different peaks in the spectrum. For example, in ethanol (CH3CH2OH) there are three different types of protons :

Start

• 1
• 2
• 3

«»

Therefore, the N.M.R. spectrum shows three groups of peaks, each group caused by a different group of protons.

The area under a group of peaks is directly proportional to the number of protons resonating to cause that peak. So, the relative areas reveal the relative amounts of protons in the molecule. For example, in ethanol there are three groups of peaks with area ratios of 1:2:3; therefore, the ratio of the different protons in ethanol is 1:2:3.

Protons on adjacent carbon atoms interact with one-another. This causes what should be a single peak for each group of protons to be split into a group of peaks.

The so-called splitting patterns depend on the number of neighbouring protons and follow the pattern in the table below :

number of neighbouring protons :	splitting pattern (relative peak heights):
0				1
1			1		1
2		1		2		1
3	1		3		3		1

So, if a proton has no neighbours it is not split at all (it is a singlet peak); one neighbouring proton gives rise to a doublet; two neighbouring protons cause atriplet and three neighbouring protons yield a quartet.

The one exception to this rule is that labile protons (see below) do not generally interact with neighbouring protons and so do not cause splitting nor are split themselves.

Putting all this information together enables the structure of the molecule to be deduced.  Even fine structural elements such as structural and E-Z isomerism can be seen.

(2) Predicting spectra :

This process is simply the reverse of the steps above. The table is consulted to find the correct δ values and the structure shows how many neighbouring protons each peak has and therefore what the splitting patterns should be.

(3) Use of D2O in N.M.R. :

Protons attached to oxygen and nitrogen atoms are easily removed and replaced by protons from other sources. This process is continual and generally goes unnoticed.  These protons are called labile.

If an organic molecule containing hydroxyl(-OH), carboxylic acid (-COOH) or amine (-NH2) groups is mixed with deuterium oxide ("heavy" water, D2O), then the protons (1H) are replaced with deuterium atoms (2H). Since the deuterium atom has an even number of particles in its nucleus (a proton and a neutron) it does not show up in proton N.M.R.

So, if spectra are taken of a molecule before and after the use of D2O, a comparison of the two spectra can reveal any labile hydrogens in the molecule.

 amcrasto@gmail.com

http://newdrugapprovals.org/

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO