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).
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 |
//////////////////////////////
amcrasto@gmail.comhttp://newdrugapprovals.org/
DRUG APPROVALS BY DR ANTHONY MELVIN CRASTOLATUR, MAHARASHTRA, INDIA
http://en.wikipedia.org/wiki/Latur
| Latur लातूर Lattalur, Ratnapur | |
|---|---|
| City | |
 
Latur
| |
| 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 |
|
| 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
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 