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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 29 year tenure till date Aug 2016, Around 30 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 13 lakh plus views on New Drug Approvals Blog in 212 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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Ezetimibe NMR


syn2

Ezetimibe

 

 

 

 

Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
J. Org. Chem., 2013, 78 (14), pp 7048–7057
Figure

Ezetimibe (1)

 ezetimibe 1 (1.08 g, 80%) as a white solid.
Mp 164–166 °C [lit.(11) 155–157 °C];
99% ee;
[α]20D −28.1 (c 0.15, MeOH) [lit.(11) −32.6 (c 0.34, MeOH)];
1H NMR (600 MHz, DMSO-d6) δ 9.49 (1H, s), 7.28–7.24 (2H, m), 7.19–7.16 (4H, m), 7.11–7.07 (4H, m), 6.75–6.71 (2H, m), 5.25 (1H, d, J 4.3 Hz), 4.77 (1H, d, J 2.2 Hz), 4.49–4.59 (1H, m), 3.07–3.04 (1H, m) 1.84–1.66 (4H, m);
13C NMR (150 MHz, CDCl3) δ 167.8, 162.3, and 160.7 (d, JC–F 240.3 Hz), 159.3, 157.9, 157.7, 142.5, 134.4, 128.7, 128.3, 128.0, 127.9, 118.7, and 118.6 (d, JC–F 8.1 Hz), 116.3, 116.2, 115.2, and 115.0 (d, JC–F 20.7 Hz), 71.5, 60.0, 59.9, 36.8, 24.9;
HRMS (EI, TOF) m/z calcd for C24H21F2NO3 [M] 409.1489 found 409.1478. Anal. Calcd for C24H21F2NO3: C 70.41, H 5.17, F 9.28, N 3.42. Found: C 70.46, H 5.23, F 9.24, N 3.34.

(3S,4S)-4-(4-(Benzyloxy)phenyl)-1-(4-fluorophenyl)-3-((S)-3-(4-fluorophenyl)-3′-hydroxypropyl)azetidin-2-one (20)

Method 1

To a cooled (0 °C) solution of lactone 19 (2.0 g, 4 mmol) in 160 mL of dry diethyl ether was added 12 mL of 1 M solution of t-BuMgCl in diethyl ether. After 2 h, 30 mL of aq NH4Cl was added. The aqueous layer was extracted with ether (160 mL), the organic layer was washed with satd NaHCO3 (50 mL) and dried (MgSO4), and the solvent was removed under reduced pressure. Crude product 20 (1.64 g, 82%) obtained as a yellowish solid was used in the next step without further purification. An analytic sample was obtained by chromatography on silica gel (hexanes/ethyl acetate 7:3). Mp 130–133 °C [lit.(11) 132–134 °C]; [α]20D −42.2 (c 1.2, CHCl3); 1H NMR (600 MHz, CDCl3) δ 7.42–7.20 (11H, m), 7.02–6.90 (6H, m), 5,04 (2H, s), 4.72–4.68 (1H, m), 4.55 (1H, d J 2.2 Hz), 3.07 (1H, dt J 7.1, 2.2 Hz), 2.05–1.93 (3H, m) 1.89–1.82 (2H, m); 13C NMR (150 MHz, CDCl3) δ 167.6, 163.0, and 161.4 (d, JC–F 244.2 Hz), 159.8 and 158.1 (d, JC–F 241.8 Hz), 159.0, 140.0, 139.9, 136.6, 133.9, and 133.8 (d, JC–F 2.9 Hz), 129.6, 128.6, 128.1, 127.5, 127.4 and 127.4, (d, JC–F 8.0 Hz), 127.2, 118.4, 118.3, 115.8, 115.8, and 115.7 (d, JC–F 22.0 Hz), 115.5, 115.4, and 115.3 (d, JC–F 21.3 Hz), 73.3, 70.1, 61.1, 60.3, 36.5, 25.0; HRMS (ESI, TOF) m/z calcd for C31H27F2NO3Na [M + Na]+ 522.1851, found 522.1862; IR (KBr) v 3441, 1743, 1609, 1510 cm–1. Anal. Calcd for C31H27F2NO3: C 74.53, H 5.45, N 2.80, F 7.61. Found: C 74.40, H 5.53, N 2.74, F 7.56.
Abstract Image
Org. Process Res. Dev., 2009, 13 (5), pp 907–910
DOI: 10.1021/op900039z
Figure

Preparation of 1-(4-Fluorophenyl)-3-(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone 1 (Ezetimibe)

 of compound 1. 1H NMR (300 MHz, DMSO-d6, δ) 1.72−1.84 (m, 4H), 3.08 (m, 1H), 4.45 (m, 1H), 4.8 (d, 1H, J = 2.0 Hz), 5.25 (d, 1H, J = 4.8), 6.75 (d, 2H, J = 8.4 Hz), 7.05−7.4 (m, 10H, Ar), 9.48 (s, 1H); IR: 3270.0, 2918, 1862, 1718.4, 1510 cm−1. MS: m/z 409.2 (M+). Anal. Calcd for C15H17NO5: C, 70.41; H, 5.17; N, 3.42. Found: C, 70.38; H, 5.27; N, 3.34.

Preparation of (3R,4S)-1-(4-Fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone 10

compound 9 as a white solid. 1H NMR (200 MHz, DMSO-d6, δ) 1.6−1.9 (m, 4H), 2.0−2.2 (bs, 1H), 3.0−3.2 (m, 1H), 4.4−4.6 (m, 1H), 4.74 (m, 1H), 5.05 (s, 2H), 6.95−7.9 (m, 17H, Ar); IR: 3492, 2922, 2852, 1719 cm−1; MS: m/z 499.3 (M+).
 ….

Synthesis of ezetimibe and desfluoro ezetimibe impurity.

Scheme 1.

Synthesis of ezetimibe and desfluoro ezetimibe impurity.

Comparison of 1H, 13C and 19F NMRs of ezetimibe and desfluoro ezetimibe ...

Fig. 4.Structures of ezetimibe, desfluoro impurity and intermediates.

Fig. 2.

Structures of ezetimibe, desfluoro impurity and intermediates.

 

 

Comparison of 1H, 13C and 19F NMRs of ezetimibe and desfluoro ezetimibe impurity.

Table 2.1H and 13C NMR assignments for Eze-1 and desfluoro Eze-1.

Positiona 1H–δ ppm


13C–δ ppm (DEPT)


Eze-1b Desfluoro Eze-1b Eze-1b Desfluoro Eze-1b
1 10.15 (br, OH) 10.13 (br, OH)
2 161.3 (C) 161.3 (C)
3 6.87 (d, J=8.5 Hz, 2H) 6.87 (dd, J=8.4, 1.8 Hz, 2H) 116.3 (2CH) 116.3 (2CH)
4 7.74 (d, J=8.5 Hz, 2H) 7.75 (dd, J=8.4, 1.8 Hz, 2H) 131.4 (2CH) 131.4 (2CH)
5 128.1 (C) 128.2 (C)
6 8.43 (s, 1H) 8.43 (s, 1H) 160.8 (CH) 160.8 (CH)
7 149.0 (d, 4J=2.6 Hz, C) 152.7 (C)
8 7.15–7.26 (m, 4H) 7.36 (dd, J=8.1, 7.5 Hz, 2H) 123.3 (d, 3J=8.4 Hz, 2CH) 121.6 (2CH)
9 7.17 (d, J=7.8 Hz, 2H) 116.5 (d, 2J=22 Hz, 2CH) 129.8 (2CH)
10 7.18 (t, J=6.3 Hz, 1H) 160.8 (d, 1J=242 Hz, C) 126.0 (CH)
Assignments: s: singlet; d: doublet; t: triplet; m: multiplet; br: broad singlet. Mean values used for coupled signals.

aNumbering of all compounds shown in Fig. 2 and copies of NMR spectra are presented in Appendix A.
bSolvent is DMSO-d6.

 

R-Enantiomer in Ezetimibe

R-Enantiomer in Ezetimibe

ABOVE 1H NMR OF R ENANTIOMER

Isolation and Characterization of R-Enantiomer in Ezetimibe

by K Chimalakonda – ‎2013 – ‎Related articles
HPLC1H and 13C NMR. The purity of isolated R-Isomer is about 98%. Keywords: Isolation; Characterization; (R)-Isomer; Ezetimibe; Supercritical Fluid  …
 

http://file.scirp.org/Html/10-2200417_36901.htm

1H NMR VALUES FOR R ENANTIOMER

 
13C NMR OF R ENANTIOMER
 
 



13C NMR VALUES OF R ENANTIOMER



 
 
 
IR OF R ENANTIOMER

Ezetimibe for reference
Ezetimibe
Ezetimibe
Ezetimibe.svg
Systematic (IUPAC) name
(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one
Clinical data
Trade names Zetia
AHFS/Drugs.com monograph
MedlinePlus a603015
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability 35–65%
Protein binding >90%
Metabolism Intestinal wall, hepatic
Half-life 19–30 hours
Excretion Renal 11%, faecal 78%
Identifiers
CAS number 163222-33-1 Yes
ATC code C10AX09
PubChem CID 150311
DrugBank DB00973
ChemSpider 132493 Yes
UNII EOR26LQQ24 Yes
KEGG D01966 Yes
ChEBI CHEBI:49040 Yes
ChEMBL CHEMBL1138 Yes
Chemical data
Formula C24H21F2NO3 
Molecular mass 409.4 g·mol−1
Physical data
Melting point 164 to 166 °C (327 to 331 °F)
 Yes (what is this?)  (verify)

1H NMR OF R ENANTIOMER PREDICTED

Ezetimibe NMR spectra analysis, Chemical CAS NO. 163222-33-1 NMR spectral analysis, Ezetimibe H-NMR spectrum

13C NMR OF R ENANTIOMER PREDICTED

Ezetimibe NMR spectra analysis, Chemical CAS NO. 163222-33-1 NMR spectral analysis, Ezetimibe C-NMR spectrum
cosy

.

Ezetimibe has the chemical name 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-2-azetidinone (hereinafter referred to by its adopted name “ezetimibe”) and is structurally represented by Formula I.
Figure US20070049748A1-20070301-C00001
Ezetimibe is in a class of lipid lowering compounds that selectively inhibit the intestinal absorption of cholesterol and related phytosterols. It is commercially available in products sold using the trademark ZETIA as a tablet for oral administration containing 10 mg of ezetimibe, and in combination products with simvastatin using the trademark VYTORIN.
U.S. Pat. No. 6,096,883 discloses generically and specifically ezetimibe and its related compounds along with their pharmaceutical compositions. The patent also describes a process for the preparation of ezetimibe.
The process described in the patent involves the use of methyl-4-(chloroformyl) butyrate and also involves isolation of the compound (3R,4S)-1-(4-fluorophenyl)-3-[3-(chloroformyl)-3-oxo-propyl]-4-(4-benzyloxyphenyl)-2-azetidinone as an intermediate. Chlorinated compounds are unstable and difficult to handle in large scale productions. The process described in the patent also involves the purification of intermediates using column chromatography, thus making the process difficult to be scaled up.
Processes for preparation of ezetimibe and its intermediates have also been described in U.S. Pat. Nos. 6,207,822, 5,856,473, 5,739,321, and 5,886,171, International Application Publication No. WO 2006/050634, and in Journal of Medicinal Chemistry 1998, 41, 973-980, Journal of Organic Chemistry 1999, 64, 3714-3718, and Tetrahedron Letters, 44(4), 801-804.

http://www.google.com/patents/US20070049748

EXAMPLE 10 PREPARATION OF 1-(4-FLUOROPHENYL)-3(R)-[3-(4-FLUOROPHENYL)-3(S)-HYDROXYPROPYL]-4(S)-(4-HYDROXYPHENYL)-2-AZETIDINONE (FORMULA I)

50 g of (3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(s)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone and 475 ml of methanol were taken into a round bottom flask. A mixture of 15 g of 5% palladium on carbon and 25 ml of water was added to it. The reaction mass was flushed with hydrogen gas and a hydrogen pressure of 3 to 5 kg/cm2 was applied. The reaction mass was stirred for 3 hours. Reaction completion was checked using thin layer chromatography. After the reaction was completed, the pressure was released and the reaction mass was filtered through perlite. The filter bed was washed with 100 ml of methanol. The filtrate was distilled completely at 70° C., and 400 ml of isopropanol was added to it. The reaction mass was heated to 45° C. and maintained for 10 minutes. The reaction mass was then allowed to cool to 28° C. 400 ml of water was added to the reaction mass and stirred for 1 hour, 20 minutes. The separated compound was filtered and washed with 100 ml of water. The wet cake was taken into another round bottom flask and 500 ml of chlorobenzene and 40 ml of methanol were added to it. The reaction mass was heated to 65° C. and maintained for 15 minutes. 25 ml of water was added to the reaction mass and stirred for 2 hours. The separated compound was filtered and washed with 100 ml of chlorobenzene. The wet cake was taken into another round bottom flask and 375 ml of chlorobenzene, and 30 ml of methanol were added to it. The reaction mass was heated to 62° C. and maintained for 10 minutes. The reaction mass was then cooled to 28° C. and 20 ml of water was added to it. The reaction mass was stirred for 20 minutes and then filtered and washed with 100 ml of chlorobenzene. The wet cake was taken into another round bottom flask and 400 ml of isopropanol was added to it. The reaction mass was heated to 46° C. and maintained for 15 minutes. 800 ml of water was added to the reaction mass at 45 to 46° C. and stirred for one hour. The separated solid was filtered and washed with water. The process of recrystallization in a combination of isopropanol and water was repeated and the obtained compound was dried at 70° C. for 5 hours to get 19.8 g of the title compound. (Yield 49.2%)
Purity by HPLC: 99.68%.

EXAMPLE 11 PURIFICATION OF 1-(4-FLUOROPHENYL)-3(R)-[3-(4-FLUOROPHENYL)-3(S)-HYDROXYPROPYL]-4(S)-(4-HYDROXYPHENYL)-2-AZETIDINONE (FORMULA I)

15.0 g of ezetimibe obtained above and 120 ml of isopropanol were taken into a round bottom flask and the reaction mass was heated to 48° C. The reaction mass was filtered through a perlite bed in the hot condition to make the solution particle free. The filtrate was taken into another round bottom flask and heated to 47° C. 240 ml of water was added at 47° C. After completion of the addition, the reaction mass was maintained at 47° C. for 1 hour. The separated solid was filtered and washed with 30 ml of water. The wet compound was dried at 70° C. for 8 hours to get 13.4 g of the title compound. (Yield 89%)
Purity by HPLC: 99.92.
benzyl ezetimibe impurity: less than 0.0003 area-%,
benzyl ezetimibe diol impurity: 0.004 area-%,
lactam cleaved alcohol impurity: 0.003 area-%,
lactam cleaved acid impurity: 0.01 area-%,
ezetimibe diol impurity: less than 0.0007 area-%.
Residual solvent content by gas chromatography:
Isopropyl alcohol: 1454 ppm
All other solvents: Less than 100 ppm.
WO1997045406A1 * May 28, 1997 Dec 4, 1997 Schering Corp 3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones
WO2004099132A2 May 5, 2004 Nov 18, 2004 Ram Chander Aryan Process for the preparation of trans-isomers of diphenylazetidinone derivatives
WO2008032338A2 * Sep 10, 2007 Mar 20, 2008 Reddy Maramreddy Sahadeva Improved process for the preparation of ezetimibe and its intermediates
EP0720599A1 Sep 14, 1994 Jul 10, 1996 Schering Corporation Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents
US20070049748 Aug 25, 2006 Mar 1, 2007 Uppala Venkata Bhaskara R Preparation of ezetim
Citing Patent Filing date Publication date Applicant Title
US7470678 Jul 1, 2003 Dec 30, 2008 Astrazeneca Ab Diphenylazetidinone derivatives for treating disorders of the lipid metabolism
US7842684 Apr 25, 2007 Nov 30, 2010 Astrazeneca Ab Diphenylazetidinone derivatives possessing cholesterol absorption inhibitor activity
US7863265 Jun 19, 2006 Jan 4, 2011 Astrazeneca Ab N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[(2R or S)-2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-D-lysine, used as anticholesterol agents
US7871998 Dec 21, 2004 Jan 18, 2011 Astrazeneca Ab Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity
US7893048 Jun 21, 2006 Feb 22, 2011 Astrazeneca Ab 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions
US7906502 Jun 21, 2006 Mar 15, 2011 Astrazeneca Ab 2-azetidinone derivatives as cholesterol absorption inhibitors for the treatment of hyperlipidaemic conditions
US8013150 * Feb 17, 2006 Sep 6, 2011 Msn Laboratories Ltd. Process for the preparation of ezetimibe
US8383810 Dec 12, 2011 Feb 26, 2013 Merck Sharp & Dohme Corp. Process for the synthesis of azetidinones
US20110130378 * May 26, 2009 Jun 2, 2011 Lek Pharmaceuticals D.D. Ezetimibe process and composition
US20110183956 * Jul 29, 2009 Jul 28, 2011 Janez Mravljak Process for the synthesis of ezetimibe and intermediates useful therefor
EP2128133A1 May 26, 2008 Dec 2, 2009 Lek Pharmaceuticals D.D. Ezetimibe process and composition
WO2008096372A2 * Feb 6, 2008 Aug 14, 2008 Pranav Gupta Process for preparing highly pure ezetimibe using novel intermediates
WO2009150038A1 May 26, 2009 Dec 17, 2009 Lek Pharmaceuticals D.D. Process for the preparation of ezetimibe and composition containing it
WO2009157019A2 * Jun 23, 2009 Dec 30, 2009 Ind-Swift Laboratories Limited Process for preparing ezetimibe using novel allyl intermediates
WO2005021497A2 * Aug 27, 2004 Mar 10, 2005 Eduardo J Martinez Tethered dimers and trimers of 1,4-diphenylazetidn-2-ones
WO2006127893A2 * May 25, 2006 Nov 30, 2006 Microbia Inc Processes for production of 4-(biphenylyl)azetidin-2-one phosphonic acids
WO2008096372A2 * Feb 6, 2008 Aug 14, 2008 Pranav Gupta Process for preparing highly pure ezetimibe using novel intermediates
US20070049748 * Aug 25, 2006 Mar 1, 2007 Uppala Venkata Bhaskara R Preparation of ezetimibe
/////
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VILAZODONE SPECTRAL DATA


Vilazodone3Dan.gif

VILAZODONE

Vilazodone hydrochloride.png

Vilazodone hydrochloride; 163521-08-2; Vilazodone HCl; Viibryd; UNII-U8HTX2GK8J; EMD-68843

NO SYNTHESIS IS THIS POST, ONLY SPECTRAL DATA DISCUSSED

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Vilazodone (United States trade name Viibryd veye-brid) is a serotonergic antidepressant developed by Clinical Data for the treatment of major depressive disorder. The chemical compound was originally developed by Merck KGaA (Germany).[2] Vilazodone was approved by the FDA for use in the United States to treat major depressive disorder in 2011.[3][4][5]

Medical uses

According to two eight-week, randomized, double-blind, placebo-controlled trials in adults, vilazodone elicits an antidepressant response after one week of treatment. After eight weeks, subjects assigned to vilazodone 40 mg daily dose (titrated over 2 weeks) experienced a significantly higher response rate than the group given placebo (44% vs 30%, P = .002). Remission rates for vilazodone were not significantly different versus placebo.[6]

According to an article on the United States approval of vilazodone written by FDA staff, “it is unknown whether [vilazodone] has any advantages compared to other drugs in the antidepressant class.”[7]

PAPER FROM OPRD

Scale-Up Synthesis of Antidepressant Drug Vilazodone

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P. R. China
Org. Process Res. Dev., 2012, 16 (9), pp 1552–1557
DOI: 10.1021/op300171m
Abstract Image

A scale-up synthesis of antidepressant drug vilazodone was accomplished in five steps. Friedel–Crafts acylation of 1-tosyl-1H-indole-5-carbonitrile with 4-chlorobutyryl chloride, selective deoxygenation in NaBH4/CF3COOH system coupled with ethyl 5-(piperazin-1-yl)-benzofuran-2-carboxylate hydrochloride, one-step deprotection and esterolysis, and the final ammonolysis led to the target molecule vilazodone in 52.4% overall yield and 99.7% purity. This convenient and economical procedure is remarkably applicable for scale-up production.

5-(4-(3-(5-Cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxamide (1)

To a solution of 6 (3 kg, 11.3 mol) in anhydrous DMF (150 L) at 15 °C was added CDI (1.6 kg, 10.2 mol). ……………………………………………….DELETED……………………to furnish the crude product of vilazodone hydrochloride 1 as off-white solid. The product of vilazodone hydrochloride was then recrystallized from an ethanol–methanol solution (1:1; 10 L) to give the final pure product vilazodone hydrochloride as white needles (2.4 kg, 81%). HPLC analysis: 99.7%. Mp: 234–236 °C (became charred).
Figure
1H NMR (500 MHz, DMSO-d6):
δ = 11.49 (s, 1H),
11.81 (bs, 1H),
8.10 (s, 1H),
7.61 (brs, 1H),
7.53 (d, J = 8.2 Hz, 1H),
7.52 (d, J = 8.2 Hz, 1H),
7.45 (d, J = 0.65 Hz, 1H),
7.41 (dd, J = 8.4 Hz, J = 1.6 Hz, 1H),
7.40 (d, J = 2.6 Hz, 1H),
7.27 (d, J = 2.4 Hz, 1H),
7.21 (dd, J = 9.1 Hz, J = 2.4 Hz, 1H),
3.78–3.70 (m, 2H), 3.58–3.52 (m, 2H),
3.23–3.21 (m, 6H),
2.78 (t, J = 7.5 Hz, 2H),
1.85–1.78 (m, 2H),
1.61–1.75 (m, 2H).
MS (ESI, 70 eV): m/z = 442 [M + H]+.
IR (KBr): 3458,
3128,
2216, NITRILE
1674, AMIDE
1597, 1400, 934 cm–1.
13C NMR (75 MHz, DMSO-d6): 22.9, 23.6, 26.8, 46.9 (2C), 50.9 (2C), 55.4, 100.1, 108.5, 109.8, 112.2, 112.7, 115.3, 118.5, 121.0, 123.6, 124.1, 125.1, 126.9, 127.7, 138.0, 146.7, 149.5, 149.6, 160.0.
HRMS (ESI): m/z [M + H]+ calcd for C26H28N5O2, 442.2238; found, 442.2234.
……………
WILL BE UPDATED
1H NMR PREDICT
VILA 1
VILA 1 VALUES VILA 1H NMR PREDICT
13 C NMR PREDICT
VILA 0
will post a clear picture soon
 
13C carbon NMR spectra

…………………………

SEE MORE SPECTROSCOPY DATA AT………..http://orgspectroscopyint.blogspot.in/2015/06/vilazodone.html

VIIBRYD Tablets for oral administration contain polymorph Form IV vilazodone hydrochloride (HCl), a selective serotonin reuptake inhibitor and a 5HT1A receptor partial agonist.

Vilazodone HCl is 2-benzofurancarboxamide, 5-[4-[4-(5cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-, hydrochloride (1:1). Its molecular weight is 477.99. The structural formula is:

VIIBRYD® (vilazodone HCl) Structural Formula Illustration

In addition to the active ingredient, VIIBRYD Tablets contain lactose monohydrate, microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, FD&C Blue #1 (40 mg only), FD&C Yellow #6 (20 mg only) and FD&C Red #40 (10 mg only).

REFERENCES
  1. “VIIBRYD (vilazodone hydrochloride) tablet VIIBRYD (vilazodone hydrochloride) kit [Forest Laboratories, Inc.]”. DailyMed. Forest Laboratories, Inc. December 2012. Retrieved28 October 2013.
  2.  “Clinical Data’s Vilazodone Patient Enrollment Over One Third Complete”. Business Wire. Berkshire Hathaway. 17 August 2006. Retrieved 12 April 2014.
  3.  “FDA approves Clinical Data Inc’s antidepressant”. Reuters. January 22, 2011.
  4.  “FDA approves Clinical Data Inc’s antidepressant”. Reuters. January 22, 2011. Retrieved 12 April 2014.
  5.  “Clinical Data, Inc. – Clinical Data, Inc. Submits New Drug Application for Vilazodone for the Treatment of Major Depressive Disorder”. Retrieved 12 April 2014.
  6. Wang, SM; Han, C; Lee, SJ; Patkar, AA; Masand, PS; Pae, CU (August 2013). “A review of current evidence for vilazodone in major depressive disorder.”. International Journal of Psychiatry in Clinical Practice 17 (3): 160–9. doi:10.3109/13651501.2013.794245. PMID 23578403.
  7.  Laughren TP, Gobburu J, Temple RJ, Unger EF, Bhattaram A, Dinh PV, Fossom L, Hung HM, Klimek V, Lee JE, Levin RL, Lindberg CY, Mathis M, Rosloff BN, Wang SJ, Wang Y, Yang P, Yu B, Zhang H, Zhang L, Zineh I (September 2011). “Vilazodone: clinical basis for the US Food and Drug Administration’s approval of a new antidepressant”. The Journal of Clinical Psychiatry 72 (9): 1166–73. doi:10.4088/JCP.11r06984. PMID 21951984.

9-(5-oxotetrahydrofuran-2-yl)nonanoic acid methyl ester


9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl ester

353
Name 9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl ester
Synonyms
Name in Chemical Abstracts 2-Furannonanoic acid, tetrahydro-5-oxo-, methyl ester
CAS No 22623-86-5
Molecular formula C14H24O4
Molecular mass 256.35
SMILES code O=C1OC(CC1)CCCCCCCCC(=O)OC

1H NMR

1H NMR

1H-NMR: 9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl ester
500 MHz, CDCl3
delta [ppm] mult. atoms assignment
1.24-1.45 m 10 H 4-H, 5-H, 6-H, 7-H, 8-H
1.57 m 2 H 3-H
1.70 m 1 H 9-H
1.82 m 1 H 9-H
2.27 t 2 H 2-H
2.30 m 2 H 3-H (ring)
2.50 m 2 H 4-H (ring)
3.67 s 3 H O-CH3
4.48 m 1 H 2-H (ring)

NMR XXX

13C NMR

13C NMR

13C-NMR: 9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl ester
125.7 MHz, CDCl3
delta [ppm] assignment
24.9 C3
25.2 C9
28.0-29.2 C4, C5, C6, C7, C8, C3 (ring)
34.0 C2
35.5 C4 (ring)
51.4 O-CH3
81.0 C2 (ring)
174.2 C1 (O-C(=O)-)
177.2 C5 (O-C(=O)-, ring)
76.5-77.5 CDCl3

13C XXX

IR

IR

IR: 9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl ester
[Film, T%, cm-1]
[cm-1] assignment
2931, 2856 aliph. C-H valence
1776 C=O valence, lactone
1737 C=O valence, ester
Cu
10-Undecenoic acid methyl esterIodoacetic acid ethyl esterreacts to9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl esterIodoethane

Synthesis of 9-(5-oxotetrahydrofuran-2-yl)nonanoic acid methyl ester

Reaction type: addition to alkenes, radical reaction, ring closure reaction
Substance classes: alkene, halogencarboxylic acid ester, lactone
Techniques: working with cover gas, stirring with magnetic stir bar, heating under reflux, evaporating with rotary evaporator, filtering, recrystallizing, heating with oil bath
Degree of difficulty: Easy

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Operating scheme

Operating schemeInstructions

http://www.oc-praktikum.de/nop/en/instructions/pdf/4005_en.pdf

Instruction (batch scale 100 mmol)

Equipment 250 mL two-neck flask, protective gas supply, reflux condenser, heatable magnetic stirrer, magnetic stir bar, rotary evaporator, Buechner funnel, suction flask, desiccator, oil bath Substances undecenoic acid methyl ester (bp 248 °C) 19.8 g (22.3 mL, 100 mmol) iodoacetic acid ethyl ester (bp 73-74 °C/ 21 hPa) 27.8 g (15.4 mL, 130 mmol) copper powder (finely powdered, >230 mesh ASTM) 30.5 g (480 mmol) tert-butyl methyl ether (bp 55 °C) 130 mL petroleum ether (bp 60-80 °C) 300 mL Reaction In a 250 mL two-neck flask with magnetic stir bar and a reflux condenser connected with a protective gas piping 19.8 g (22.3 mL, 100 mmol) undecenoic acid methyl ester and 27.8 g (15.4 mL, 130 mmol) iodoacetic acid ethyl ester are mixed with 30.5 g (480 mmol) copper powder under a protective gas atmosphere. Afterwards the reaction mixture is stirred at 130 °C oil bath temperature under protective gas for 4 hours. (Reaction monitoring see Analytics.)

Work up The reaction mixture is cooled down to room temperature, 30 mL tert-butyl methyl ether are added, the mixture is stirred for 5 minutes and filtered off. The copper powder on the filter is washed four times with 25 mL tert-butyl methyl ether each. Filtrates and wash solutions are combined, the solvent is evaporated at the rotary evaporator. A yellow oil remains as crude product. Crude yield: 25.4 g.

The crude product is dissolved in 300 mL petroleum ether under reflux. The solution is allowed to cool down to room temperature, then it is stored in the refrigerator over night for complete crystallization. The crystalline product is sucked off over a Buechner funnel and dried in the vacuum desiccator. The mother liquor is stored again in the refrigerator for a check of complete crystallization. Yield: 19.5 g (76.1 mmol, 76%); white solid, mp 34 °C Comments In order to achieve a quantitative reaction within 4 hours, a fivefold excess of copper is used.

Waste management Recycling The copper powder can be used three times.

Waste disposal Waste Disposal evaporated tert-butyl methyl ether (might contain iodoethane) organic solvents, containing halogen mother liquor from recrystallization organic solvents, containing halogen copper powder solid waste, free from mercury, containing heavy metals

Time 6-7 hours

Break After heating and before recrystallizing

Degree of difficulty Easy

Analytics Reaction monitoring with TLC Sample preparation: Using a Pasteur pipette, two drops of the reaction mixture are taken and diluted with 0.5 mL diethyl ether. TLC-conditions: adsorbant: TLC-aluminium foil (silica gel 60) eluent: petroleum ether (60/80) : acetic acid ethyl ester = 7 : 3 visualisation: The TLC-aluminium foil is dipped in 2 N H2SO4 and then dried with a hot air dryer. Reaction monitoring with GC Sample preparation: Using a Pasteur pipette, one drop of the reaction mixture is taken and diluted with 10 mL dichloromethane. From this solution, 0.2 µL are injected. 10 mg from the solid product are dissolved in 10 mL dichloromethane. From this solution, 0.2 µL are injected. GC-conditions: column: DB-1, 28 m, internal diameter 0.32 mm, film 0.25 µm inlet: on-column-injection carrier gas: hydrogen (40 cm/s) oven: 90 °C (5 min), 10 °C/min to 240 °C (40 min) detector: FID, 270 °C Percent concentration was calculated from peak areas.

Chromatogram

crude product chromatogram

GC: crude product
column DB-1, L=28 m, d=0.32 mm, film=0.25 µm
inlet on column injection, 0.2 µL
carrier gas H2, 40 cm/s
oven 90°C (5 min), 10°C/min –> 240°C (40 min)
detector FID, 270°C
integration percent concentration calculated from relative peak area

pure product chromatogram

GC: pure product
column DB-1, L=28 m, d=0.32 mm, film=0.25 µm
inlet on column injection, 0.2 µL
carrier gas H2, 40 cm/s
oven 90°C (5 min), 10°C/min –> 240°C (40 min)
detector FID, 270°C
integration percent concentration calculated from relative peak area

Substances required

Batch scale: 0.01 mol 0.1 mol 10-Undecenoic acid methyl ester
Educts Amount Risk Safety
10-Undecenoic acid methyl ester
19.8 g H- EUH- P-
Iodoacetic acid ethyl ester
GHS06 GHS05 Danger
27.8 g H300 H314 EUH- P264 P280 P305 + 351 + 338 P310
Reagents Amount Risk Safety
Copper powder
GHS09 Warning
30.5 g H400 EUH- P273
Solvents Amount Risk Safety
tert-Butyl methyl ether
GHS02 GHS07 Danger
130 mL H225 H315 P210
Petroleum ether (60-80)
GHS02 GHS08 GHS07 GHS09 Danger
300 mL H225 H304 H315 H336 H411 EUH- P210 P261 P273 P301 + 310 P331
Others Amount Risk Safety
Sulfuric acid 2N
GHS05 Danger
H314 H290 EUH- P280 P301 + 330 + 331 P305 + 351 + 338 P309 + 310
Solvents for analysis Amount Risk Safety
Petroleum ether (60-80)
GHS02 GHS08 GHS07 GHS09 Danger
H225 H304 H315 H336 H411 EUH- P210 P261 P273 P301 + 310 P331
Acetic acid ethyl ester
GHS02 GHS07 Danger
H225 H319 H336 EUH066 P210 P261 P305 + 351 + 338
Dichloromethane
GHS08 GHS07 Warning
H351 H315 H319 H335 H336 H373 P261 P281 P305 + 351 + 338

Substances produced

Batch scale: 0.01 mol 0.1 mol 10-Undecenoic acid methyl ester
Products Amount Risk Safety
9-(5-Oxotetrahydrofuran-2-yl)nonanoic acid methyl ester

Equipment

Batch scale: 0.01 mol 0.1 mol 10-Undecenoic acid methyl ester
two-necked flask 250 mL two-necked flask 250 mL protective gas piping protective gas piping
reflux condenser reflux condenser heatable magnetic stirrer with magnetic stir bar heatable magnetic stirrer with magnetic stir bar
rotary evaporator rotary evaporator suction filter suction filter
suction flask suction flask exsiccator with drying agent exsiccator with drying agent
oil bath oil bath

Simple evaluation indices

Batch scale: 0.01 mol 0.1 mol 10-Undecenoic acid methyl ester
Atom economy 53.9 %
Yield 76 %
Target product mass 19.5 g
Sum of input masses 370 g
Mass efficiency 53 mg/g
Mass index 19 g input / g product
E factor 18 g waste / g product

………………

………

(1S)-(-)-beta-Pinene


(1S)-(1)-beta-Pinene Structure

(1S)-(1)-beta-Pinene, (1S)-(-)-beta-Pinene

 

.

image of (1s)-(-)-b-pinene.

 

image of (1s)-(-)-b-pinene

 

 

13C NMR

.

 

image of (1s)-(-)-b-pinene.

 

APT

image of (1s)-(-)-b-pinene.

DEPT

image of (1s)-(-)-b-pinene.

COSY

image of (1s)-(-)-b-pinene.

HETCOR

image of (1s)-(-)-b-pinene

IR

 

MASS

.

 

.

 

 

 

RAMAN

 

 

CAS No. 18172-67-3
Chemical Name: (1S)-(1)-beta-Pinene
Synonyms: β-Pinen;FEMA 2903;PINENE BETA;(1S)-(-)-B-PINENE;LAEVO-BETA-PINENE;(1s)-(-)-á-pinene;ALPHA,BETA-PINENE;(1S)-(-)-SS-PINENE;PINENE, (1S)-(-)-B-;(1s)-(1)-beta-pinene
CBNumber: CB8270232
Molecular Formula: C10H16
Formula Weight: 136.23
MOL File: 18172-67-3.mol
(1S)-(1)-beta-Pinene Property
mp : −61 °C(lit.)
bp : 165-167 °C(lit.)
alpha : -18.5 º (c=neat 25 ºC)
density : 0.866 g/mL at 25 °C
vapor density : 4.7 (vs air)
vapor pressure : ~2 mm Hg ( 20 °C)
FEMA : 2903
refractive index : n20/D 1.478
Fp : 91 °F
storage temp. : 2-8°C
Water Solubility : insoluble
Merck : 14,7446
BRN : 2038282
CAS DataBase Reference: 18172-67-3(CAS DataBase Reference)
NIST Chemistry Reference: Bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-, (1S)-(18172-67-3)
EPA Substance Registry System: Bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-, (1S,5S)-(18172-67-3)
Safety
Hazard Codes : Xn,N,Xi
Risk Statements : 10-20/21/22-36/37/38-43-51-65-51/53
Safety Statements : 16-26-36/37-46-61-62
RIDADR : UN 2319 3/PG 3
WGK Germany : 3
RTECS : DT5077000
HazardClass : 3
PackingGroup : III
HS Code : 29021910

take a tour

Amalner,  Jalgaon, Maharashtra, India

Amalner – Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Amalner

Amalner, India is a city and a municipal council in Jalgaon district in the state of Maharashtra, India, situated on the bank of the Bori River. Amalner is the …

History – ‎Geography – ‎Demographics – ‎Education

Map of amalner maharashtra

 

 

10000 devout Hindus were present for the Hindu Dharmajagruti Sabha at Amalner, Maharashtra

 

end of amalner…………

 

Daulatabad Fort Market

India / Maharashtra / Aurangabad /

Daulatabad, Maharashtra – Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Daulatabad,_Maharashtra

Daulatabad also known as Devagiri is a town which includes the Devagiri-Daulatabad fort It carries the distinction of remaining undefeated in battle.

Fort of Daulatabad – ‎The City – ‎Monuments – ‎Transport
 Marketplace
 Map of daulatabad

Market place and Hotel/Dhaba
Nearby cities: Aurangabad, New Aurangabad, CIDCO. , Gangapur
Coordinates:   19°56’36″N   75°13’17″E
 

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

β-Sitosterol, 후박(厚朴)


β-Sitosterol

http://www.herbdb.co.kr/herb/dbsearch3/separation_view.asp?key=302

  C29H50O, 414.00
  White needles
m.p(℃)   283-285
IR(cm-¹) νmax (KBr): 3400, 1680
UV(nm) λmax (MeOH): 216
MS EIMS m/z: 414 [M]+

 

 

β-Sitosterol (β-谷甾醇); CAS: 83-46-5

(300 MHz, CDCl3) δ: 5.36 (1H, d, J = 5.2 Hz, H-6), 3.53 (1H, m, H-3),1.01 (3H, s, CH3-19), 0.94 (3H, d, J = 6.5 Hz, CH3-21), 0.92 (3H, d, J = 6.5 Hz,CH3-26), 0.83 (3H, t, J = 6.6 Hz, CH3-29), 0.69 (3H, s, CH3-18)

 

13c nmr

(75 MHz, CDCl3) δ: 37.2 (C-1), 32.1 (C-2), 72.0 (C-3), 42.5 (C-4), 141.0 (C-5), 121.9 (C-6), 32.1 (C-7), 31.9 (C-8), 50.4 (C-9), 36.7 (C-10), 21.3 (C-11), 40.0 (C-12), 42.5 (C-13), 57.0 (C-14), 24.5 (C-15), 28.4 (C-16), 56.3 (C-17), 12.2 (C-18), 19.2 (C-19), 36.3 (C-20), 19.0 (C-21), 34.2 (C-22), 26.4 (C-23),46.1 (C-24), 29.4 (C-25), 19.6 (C-26), 20.0 (C-27), 23.3 (C-28),12.0 (C-29)

 

 

ANAGLIPTIN Spectral visit


N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide
CAS No.: 739366-20-2
Synonyms:
  • Anagliptin;
Formula: C19H25N7O2
Exact Mass: 383.20700

Anagliptin chemically known as N-[2-[2-[2(S)-cyanopyrrolidin-l-yl]-2-oxoethylamino]- 2-methylpropyl]-2-methylpyrazolo[l,5-a]pyrimidine-6-carboxamide is represented by the structural formula:

Figure imgf000003_0001

Anagliptin is a dipeptidyl peptidase IV- inhibitor. United States Patent No 7345 1 80- (IJS’ 180) discloses anagliptin.

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide NMR spectra analysis, Chemical CAS NO. 739366-20-2 NMR spectral analysis, N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide H-NMR spectrum

N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide NMR spectra analysis, Chemical CAS NO. 739366-20-2 NMR spectral analysis, N-[2-[[2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl]amino]-2-methylpropyl]-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide C-NMR spectrum

Example 5: Synthesis of N-[2-2[2(S)-Cyano pyrrolidin-l-yl]-2-oxoethyIamino]-2- methyIpropyl]-2-methyaIpyrazoIo [1, 5-a] pyrimidine-6-carboxamide (I, anagliptin).

1H NMR (300 MHz, CDC13): δ 1.16 (s, 6H), 2.23(m, 4H), 2.54(s, 3H), 3.25-3.51 (m, 6H), 4.78 (m, 1H), 6.53 (s, 1H), 8.05 (s, 1H), 8.93 (s, 1H), 9.22(s, 1H)

HPLC Purity: 99.71%, Chiral purity: 100%………WO2014147640A2

Kato, M.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M.; Mirensha, Y.;
Kakigami, T. Discovery and pharmacological characterization of N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-
2-methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective
DPP-IV inhibitor. Bioorg. Med. Chem. 2011, 19, 7221–7227.

http://www.sciencedirect.com/science/article/pii/S0968089611007784

Full-size image (4 K)

LATUR, MAHARASHTRA, INDIA

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

Latur
लातूर
Lattalur, Ratnapur
City

Latur is located in Maharashtra

Latur
Latur

Location in Maharashtra, India

Coordinates: 18.40°N 76.56°ECoordinates18.40°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

Map of latur city

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

Omeprazole spectral visit


Omeprazole

CAS NO. 119141-89-8

(RS)-5-methoxy-2-((4-methoxy-3,5-dimethylpyridin-2-yl) methylsulfinyl)-1H-benzo[d]imidazole

Omeprazole
CAS No.: 119141-89-8
Synonyms:
  • ZOLTUM;
  • PRILOSEC;
  • LOSEC;
  • GASTROGARD;
  • ANTRA;
  • OMEPRAL;
  • MEPRAL;
  • H 168/68;
  • GASTROLOC;
  • MOPRAL;
Formula: C17H19N3O3S
Exact Mass: 345.11500

Ome is a chemical substance (C17H19N3O3S), its molecular weight is 345.42g/mol, the color is white, has weak alkaline properties, melts at 156oC

ome 1h nmr

NMR……………http://file.selleckchem.com/downloads/nmr/S138902-Omeprazole-Prilosec-HNMR-Selleck.pdf

NMR………..file:///C:/Users/anthonyc/Downloads/233-434-1-SM.pdf

1H NMR PREDICT

STR

STR 2

OMEPRAZOLE NMR spectra analysis, Chemical CAS NO. 119141-89-8 NMR spectral analysis, OMEPRAZOLE H-NMR spectrum

13C NMR PREDICT

OMEPRAZOLE NMR spectra analysis, Chemical CAS NO. 119141-89-8 NMR spectral analysis, OMEPRAZOLE C-NMR spectrum

COSY

COSY NMR prediction (7)

HMBC

HMBC, HSQC NMR prediction (1)

Image

………………………………..

Displaying image004.png

Displaying image006.png

ARKIVOC 2006 (v) 5-11

The structure of Omeprazole in the solid state: a 13C and 15N NMR/CPMAS study

Rosa M. Claramunt,a Concepción López,a and José Elguerob *

a Departamento de Química Orgánica y Bio-Orgánica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain

b Instituto de Química Médica, CSIC, Juan de la Cierva, 3. E-28006 Madrid, Spain

E-mail: iqmbe17@iqm.csic.es

http://www.arkat-usa.org/get-file/22955/

Abstract

The 13C and 15N CPMAS spectra of a solid sample of Omeprazole have been recorded and all the signals assigned. The sample consists uniquely of the 6-methoxy tautomer. For analytical purposes, the signals of the other tautomer, the 5-methoxy one, were estimated from the data in solution (Magn. Reson. Chem. 2004, 42, 712).

Keywords: Omeprazole, NMR, 13C, 15N, CPMAS, tautomerism, benzimidazole

Displaying image008.png

Omeprazole, 5(6)-methoxy-2-{(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl}-1H-benz – imidazole [1(2)], is an important ulcer drug,1 that has been classified amongst the blockbuster drugs.2 This compound presents two sources of structural differentiation. First, Omeprazole is chiral (a vs. b) 3 since it has a stereogenic center on the sulfur atom but the commercial form has been sold, until recently, as a racemate. In 2001, Esomeprazole magnesium, the S enantiomer was approved.4 The second source of diversity is that these compounds present tautomerism (1 vs. 2). We have already devoted a paper to the tautomerism of Omeprazole in solution using 1 H and 13C NMR spectroscopy.5 In this paper a complete assignment of the signals was carried out and the tautomeric equilibrium constant, KT = [2]/[1], was determined in THF at 195 K, to be 0.59 in favor of the 6-methoxy tautomer 2.

Displaying image010.png

Displaying image012.png

References

1. Carlsson, E.; Lindberg, P.; von Unge, S. Chem. Brit. 2002, 38, 42 and references therein.

2. Berkowitz, B. A.; Sachs, G. Mol. Interventions 2002, 2, 6.

3. von Unge, S.; Langer, V.; Sjölin, L. Tetrahedron: Asymmetry 1997, 8, 1967.

4. Olbe, L.; Carlsson, E.; Lindberg, P. Nature Reviews Drug Discovery 2003, 2, 132.

5. Claramunt, R. M.; López, C.; Alkorta, I.; Elguero, J.; Yang, R.; Schulman, S. Magn. Reson. Chem. 2004, 42, 712.

6. Elguero, J.; Katritzky, A. R.; Denisko, O. Adv. Heterocycl. Chem. 2000, 76. 1.

7. Allen, F. H. Acta Crystallogr. Sect. B 2002, 58, 380.

8. Braga, S. S.; Ribeiro-Claro, P.; Pillinger, M.; Gonçalves, I. S.; Fernandes, A. C.; Pereira, F.; Romåo, C. C.; Correia, P. B.; Teixeira-Dias, J. J. C. J. Incl. Phenom. Macro. Chem. 2003, 47, 47.

9. Berger, S.; Braun, S. 200 and More NMR Experiments. Wiley-VCH, Weinheim, 2004.

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DSC OF OMEPRAZOLE

UV

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UV Study: The Ultraviolet spectrum was recorded from 200 nm to 400 nm, with API concentration of 0.0015% in methanol. The spectrum showed two λmax at 207 and 301 nm. As seen below.

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FTIR Study The FTIR of spectrum of Omeprazole was recorded by preparation of pellet with KBr.

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NMR

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13 C NMR

 

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mass

The mass spectrum of Omeprazole was recorded on 4000-Q trap LCMSMS system. The sample is introduced into the system through HPLC by bypassing the column. The ESI +ve ionization spectrum of Omeprazole displayed a protonated molecular ion at m/z= 346 which corresponds to the molecular formula C17H17N3O3S. The fragmentation pattern was observed with product ion scan.

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Raman

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Title: Omeprazole
CAS Registry Number: 73590-58-6
CAS Name: 5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole
Manufacturers’ Codes: H-168/68
Trademarks: Gastrogard (Merial); Losec (AstraZeneca); Mopral (AstraZeneca); OmeLich (Winthrop); Omelind (Lindopharm); Omepral (AstraZeneca); Omeprazen (Malesci); Osiren (Probiomed); Parizac (Lacer); Pepticum (Grñenthal); Prilosec (AstraZeneca); Zegerid (Santarus); Zoltum (AstraZeneca)
Molecular Formula: C17H19N3O3S
Molecular Weight: 345.42
Percent Composition: C 59.11%, H 5.54%, N 12.16%, O 13.90%, S 9.28%
Literature References: Gastric proton-pump inhibitor. Prepn: U. K. Junggren, S. E. Sjostrand, EP 5129; eidem, US 4255431(1979, 1981 both to AB Hässle). Resolution and activity of enantiomers: P. Erlandsson et al., J. Chromatogr. 532, 305 (1990). Manuf process for optically pure salts: S. Von Unge, US 5693818 (1997 to Astra). Pharmacology: P. Muller et al., Arzneim.-Forsch. 33, 1685 (1983). Mechanism of action study: B. Wallmark et al., Biochim. Biophys. Acta 778, 549 (1984). LC determn in plasma and urine: P. Lagerstrom, B. Persson, J. Chromatogr. 309, 347 (1984). Survey of preclinical data: Scand. J. Gastroenterol. 20, Suppl 108, 1-120 (1985). Toxicological studies: L. Ekman et al., ibid. 53. Clinical trial in Zollinger-Ellison syndrome: C. B. H. W. Lamers et al., N. Engl. J. Med. 310, 758 (1984); in duodenal ulcer: K. Lauritsen et al., ibid. 312, 958 (1985). Veterinary trial in race horses: M. J. Murray et al., Equine Vet. J. 29, 425 (1997). Review of pharmacology and clinical efficacy: H. D. Langtry, M. I. Wilde, Drugs 56, 447-486 (1998).
Properties: Crystals from acetonitrile, mp 156°. Freely sol in ethanol, methanol; slightly sol in acetone, isopropanol; very slightly sol in water. LD50 in mice, rats (g/kg): 0.08, >0.05 i.v.; >4, >4 orally (Ekman).
Melting point: mp 156°
Toxicity data: LD50 in mice, rats (g/kg): 0.08, >0.05 i.v.; >4, >4 orally (Ekman)
Derivative Type: Magnesium salt
CAS Registry Number: 95382-33-5
Trademarks: Antra (AstraZeneca); Gastracid (AWD); Gastroloc (AstraZeneca); Omebeta (Betapharm); Omep (Hexal); Ome-Puren (Alpharma)
Molecular Formula: C34H36MgN6O6S2
Molecular Weight: 713.12
Percent Composition: C 57.26%, H 5.09%, Mg 3.41%, N 11.78%, O 13.46%, S 8.99%
Derivative Type: S-Form
CAS Registry Number: 119141-88-7
Additional Names: Esomeprazole; perprazole
Manufacturers’ Codes: H-199/18
Literature References: LC-MS determn in plasma: H. Stenhoff et al., J. Chromatogr. B 734, 191 (1999).
Properties: Colorless syrup. [a]D20 -155° (c = 0.5 in chloroform).
Optical Rotation: [a]D20 -155° (c = 0.5 in chloroform)
Derivative Type: S-Form magnesium salt
CAS Registry Number: 161973-10-0
CAS Name: (T-4)-Bis[5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazolato]magnesium
Additional Names: esomeprazole magnesium
Trademarks: Nexium (AstraZeneca)
Literature References: Review of clinical experience in acid disorders: D. A. Johnson, Expert Opin. Pharmacother. 4, 253-264 (2003).
Properties: White powder. [a]D20 -128.2° (c = 1 in methanol).
Optical Rotation: [a]D20 -128.2° (c = 1 in methanol)
Therap-Cat: Antiulcerative; in treatment of Zollinger-Ellison syndrome.
Therap-Cat-Vet: Antiulcerative.
Keywords: Antiulcerative; Gastric Proton Pump Inhibitor.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.




COCK WILL TEACH YOU NMR
COCK SAYS MOM CAN TEACH YOU NMR

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Methyl (S)-aminobutyrate hydrochloride…..Levetiracetam intermediate


Methyl (S)-aminobutyrate hydrochloride…..Levetiracetam intermediate

(s)-2-aminobutyric Acid Methyl Ester
PATENT

http://www.google.im/patents/WO2003014080A2?cl=en

(S)-amino butyric acid
Step 1 – Synthesis of methyl (S)-aminobutyrate hydrochloride

……………………………(23) …………………………………………………….(24)
5.0g of (S)-amino butyric acid (23) was suspended in 50 ml of methanol and stirred at 0-5°C. 6.35g of thionyl chloride was added dropwise over 45 min to form a clear solution. After stirring for 20 hours at room temperature, the reaction was concentrated under reduced pressure to dryness and the almost colourless residue solidified to give the required product which was dried in an oven at 50°C under vacuum (7.6g; 102% crude yield). The same reaction was scaled-up from 200g of the amino acid and provided 296g (99.5% yield) of product (24). Analysis gave the following results:
1H NMR (DMSO-de) : d 0.94 (3H, t) 1.88 (2H, q) 3.75 (3H, s) 3,9 (1H, m) 8,8
(3H, m). m.p. : 107°C-110°C IR : 2876 cm 1, 1742 cm 1.
TLC : Si02, 20%MeOH/80%EtOAc/ l%NH OH, UV & IR. (TLC is an abbreviation for thin layer chromatography).
logo
1H NMR PREDICT
(S)-2-aminobutyric acid methyl ester NMR spectra analysis, Chemical CAS NO. 15399-22-1 NMR spectral analysis, (S)-2-aminobutyric acid methyl ester H-NMR spectrum
13C PREDICT
logo
(S)-2-aminobutyric acid methyl ester NMR spectra analysis, Chemical CAS NO. 15399-22-1 NMR spectral analysis, (S)-2-aminobutyric acid methyl ester C-NMR spectrum
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.




COCK WILL TEACH YOU NMR
COCK SAYS MOM CAN TEACH YOU NMR

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO …..FOR BLOG HOME CLICK HERE
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  JALGAON, MAHARASHTRA, INDIA

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MANUDEVI

(S)-2-amino-butanamide hydrochloride………. Key intermediate of Levetiracetam


(S)-2-amino-butanamide hydrochloride………. Key intermediate of Levetiracetam

(S)-2-amino-butanamide hydrochloride

Key intermediate of Levetiracetam

  • CAS Number 7682-20-4
  • Linear Formula CH3CH2CH(NH2)CONH2 · HCl
  • Displaying
Stage B
(S)-2-aminobutyramide hydrochloride Preparation

Into the above (S)-2-aminobutyric acid methyl ester hydrochloride is added Isopropanol is then added, followed by the introduction of ammonia gas at a pressure about 60 psi (413 kPa) until the reaction is complete. After filtering to remove formed ammonium chloride, the solvent is partially evaporated and isopropanol hydrochloride is added. The mixture is stirred while solid product forms, then the solid is separated by filtration and washed with isopropanol.

The product was characterized by the following 1H NMR data (200 MHz, DMSO-d6): 0.9-1.0(t,3H), 1.8-1.9(Q,2H), 3.7-3.8(t, 1H), 7.5-7.7(Br,NH2), 8.0-8.2(Br,NH2)
1H NMR PREDICT
  • (2S)-2-aminobutanamide,hydrochloride NMR spectra analysis, Chemical CAS NO. 7682-20-4 NMR spectral analysis, (2S)-2-aminobutanamide,hydrochloride H-NMR spectrum

………..

13C NMR PREDICT

(2S)-2-aminobutanamide,hydrochloride NMR spectra analysis, Chemical CAS NO. 7682-20-4 NMR spectral analysis, (2S)-2-aminobutanamide,hydrochloride C-NMR spectrum

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.
P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.



COCK WILL TEACH YOU NMR
COCK SAYS MOM CAN TEACH YOU NMR

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TIRUPATI, INDIA
Map of tirupati town.

Tirupati
తిరుపతి
City
Clockwise from top: Tirumala Venkateswara Temple, Tirumala ghat road, City skyline and Chandragiri fort

Clockwise from top: Tirumala Venkateswara Temple, Tirumala ghat road, City skyline and Chandragiri fort
Tirupati is located in Andhra Pradesh

Tirupati
Tirupati

Location in Andhra Pradesh, India

Coordinates: 13.65°N 79.42°ECoordinates: 13.65°N 79.42°E
Country India
State Andhra Pradesh
Region Rayalaseema
District Chittoor
Government
 • Member of Parliament Varaprasad Rao Velagapalli
Area
 • City 24 km2 (9 sq mi)
Elevation 161 m (528 ft)
Population (2011)[1]
 • City 287,035
 • Density 12,000/km2 (31,000/sq mi)
 • Metro[2] 459,985
Languages
 • Official Telugu
Time zone IST (UTC+5:30)
PIN 517501
Telephone code +91–877
Vehicle registration AP 03
Website Tirupati Mucnicipal Corporation

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Kapila Theertham in Tirupati



Food Service During Tirumala Tirupati Devastanam’s ‘Srinivasa Kalyanam Utsavam’ at MARG Swarnabhoomi

 

 

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