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BRUSH UP YOUR NMR, 4-(3,5-Dichloropyridin-4-yl)morpholine

March 27, 2018 11:00 am / 1 Comment on BRUSH UP YOUR NMR, 4-(3,5-Dichloropyridin-4-yl)morpholine

3,5-Dichloro-4-morpholinopyridine

Preparation of 4-(3,5-Dichloropyridin-4-yl)morpholine (5).(Pichowicz, M.; Crumpler, S.; McDonald, E.; Blagg, J. Tetrahedron 2010, 66, 2398, DOI: 10.1016/j.tet.2010.01.101)

5 as a light-orange solid.

¹H NMR (CDCl₃, 400 MHz): δ = 8.35 (2H, s), 3.84 (4H, m), 3.37 (4H, m);

¹³C NMR (CDCl₃, 101 MHz): δ = 150.8, 149.3, 128.4, 67.4, 50.4;

HRMS–ESI⁺: m/z [M + H]⁺ calcd for C₉H₁₁Cl₂N₂O⁺: 233.02429; found: 233.02446.

1H NMR PREDICT

13C NMR PREDICT

DEPT PREDICT

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.8b00009

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Clc2cncc(Cl)c2N1CCOCC1

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water

December 20, 2017 10:36 am / Leave a comment

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected [small alpha]-amino acids in water

Green Chem., 2018, Advance Article
DOI: 10.1039/C7GC02862H, Paper

Peter Olsen, Michael Oschmann, Eric V. Johnston, Bjorn Akermark
Ring opening of cyclic carbonates with unprotected amino acids in water – a route to highly functional carbamates.

Synthesis of highly functional carbamates through ring-opening of cyclic carbonates with unprotected α-amino acids in water

Peter Olsén,*^a Michael Oschmann,^a Eric V. Johnston*^a and Björn Åkermark*^a

Author affiliations

*Corresponding authors

^aDepartment of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE 106 91, Stockholm, Sweden
E-mail: peter.olsen@su.se, eric@sigridthx.com, bjorn.akermark@su.se

Abstract

The present work shows that it is possible to ring-open cyclic carbonates with unprotected amino acids in water. Fine tuning of the reaction parameters made it possible to suppress the degree of hydrolysis in relation to aminolysis. This enabled the synthesis of functionally dense carbamates containing alkenes, carboxylic acids, alcohols and thiols after short reaction times at room temperature. When Glycine was used as the nucleophile in the ring-opening with four different five membered cyclic carbonates, containing a plethora of functional groups, the corresponding carbamates could be obtained in excellent yields (>90%) without the need for any further purification. Furthermore, the orthogonality of the transformation was explored through ring-opening of divinylenecarbonate with unprotected amino acids equipped with nucleophilic side chains, such as serine and cysteine. In these cases the reaction selectively produced the desired carbamate, in 70 and 50% yield respectively. The synthetic design provides an inexpensive and scalable protocol towards highly functionalized building blocks that are envisioned to find applications in both the small and macromolecular arena.

link http://pubs.rsc.org/en/Content/ArticleLanding/2018/GC/C7GC02862H?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+rss%2FGC+%28RSC+-+Green+Chem.+latest+articles%29#!divAbstract

Affiliation

Stockholm University

Location

Stockholm, Sweden

Department

Department of Organic Chemistry

Position

PostDoc Position

Research experience

Jun 2010–Feb 2016

PhD Student

KTH Royal Institute of Technology · Department of Fibre and Polymer Technology

Sweden · Stockholm

Björn Åkermark

Education

Jan 1962–Jun 1967

KTH Royal Institute of Technology

Organic Chemistry and Catalysis · PhD

Sweden · Stockholm

Awards & achievements

Jun 2009

Award: Bror Holmberg Medal, Swedish Chemical Society
Feb 2009

Award: Ulla and Stig Holmquists Prize, Uppsala University
Oct 1997

Award: Dr hc, University D´Aix-Marseille
Oct 1991

Award: KTH Prize for Excellence in Teaching
Oct 1978

Award: Arrhenius Medal, Swedish Chemical Society
Aug 1977

Scholarship: Zorn Fellowship, Swden America Foundation
Nov 1976

Award: Letterstedt Award, Roy Swed. Acad. of Science

Dr. Eric Johnston, Ph.D.

Chief Technology Officer

Dr. Eric V. Johnston obtained his Master of Science degree in 2008 at the Department of Organic Chemistry, Stockholm University, Sweden. In the same year, he started his graduate studies under the supervision of Prof. Jan-Erling Bäckvall. During his PhD, he worked on the development of new homogeneous and heterogeneous transition-metal catalysts.

After receiving his PhD in 2012, he joined Prof. Samuel J. Danishefskys research group at Memorial Sloan-Kettering Cancer Center, New York, USA as a postdoctoral fellow supported by The Swedish Research Council. Here he was engaged in the total chemical synthesis of glycolsylated proteins that play important roles in modern cancer treatment.

In 2014 he returned to the Department of Organic Chemistry at Stockholm University to establish his own group. The goal of his research is to contribute new advances to the strategy and methodology for the preparation of synthetic macromolecules such as proteins, glycopeptides, sequence and length-controlled polymers. He is also a Co-Supervisor for Prof. Björn Åkermarks research group, which aims at studying and developing new homogeneous, as well as heterogeneous, water oxidation catalysts.

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Ezetimibe NMR

October 8, 2015 7:26 am / Leave a comment

Ezetimibe

Marcin Śnieżek, Sebastian Stecko, Irma Panfil, Bartłomiej Furman, and Marek Chmielewski *

Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland

J. Org. Chem., 2013, 78 (14), pp 7048–7057

DOI: 10.1021/jo400807c..http://pubs.acs.org/doi/full/10.1021/jo400807c

Ezetimibe (1)

ezetimibe 1 (1.08 g, 80%) as a white solid.

Mp 164–166 °C [lit.(11) 155–157 °C];

99% ee;

[α]²⁰_D −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, J_C–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, J_C–F 8.1 Hz), 116.3, 116.2, 115.2, and 115.0 (d, J_C–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]²⁰_D −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, J_C–F 244.2 Hz), 159.8 and 158.1 (d, J_C–F 241.8 Hz), 159.0, 140.0, 139.9, 136.6, 133.9, and 133.8 (d, J_C–F 2.9 Hz), 129.6, 128.6, 128.1, 127.5, 127.4 and 127.4, (d, J_C–F 8.0 Hz), 127.2, 118.4, 118.3, 115.8, 115.8, and 115.7 (d, J_C–F 22.0 Hz), 115.5, 115.4, and 115.3 (d, J_C–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.

Org. Process Res. Dev., 2009, 13 (5), pp 907–910

DOI: 10.1021/op900039z

http://pubs.acs.org/doi/abs/10.1021/op900039z

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⁺).

….

doi:10.1016/j.jpha.2015.04.002

Scheme 1.

Synthesis of ezetimibe and desfluoro ezetimibe impurity.

http://www.sciencedirect.com/science/article/pii/S2095177915000386

Fig. 4.

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.

Position^a	¹H–δ ppm		¹³C–δ ppm (DEPT)
Position^a	Eze-1^b	Desfluoro Eze-1^b	Eze-1^b	Desfluoro Eze-1^b
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	7.15–7.26 (m, 4H)	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

http://www.scirp.org/journal/PaperDownload.aspx?paperID=36901

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

163222-33-1

Ezetimibe
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
Pregnancy category	AU: C US: C
Legal status	AU: Prescription Only (S4) CA: ℞-only UK: POM US: ℞-only
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
ATC code	C10AX09
PubChem	CID 150311
DrugBank	DB00973
ChemSpider	132493
UNII	EOR26LQQ24
KEGG	D01966
ChEBI	CHEBI:49040
ChEMBL	CHEMBL1138
Chemical data
Formula	C₂₄H₂₁F₂N O₃
Molecular mass	409.4 g·mol⁻¹
SMILES [show]
InChI [show]
Physical data
Melting point	164 to 166 °C (327 to 331 °F)
(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.

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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ORGANIC SPECTROSCOPY INTERNATIONAL HAS 2 LAKH VIEWS

August 3, 2015 8:19 am / 1 Comment on ORGANIC SPECTROSCOPY INTERNATIONAL HAS 2 LAKH VIEWS

ORGANIC SPECTROSCOPY INTERNATIONAL HAS 2 LAKH VIEWS

Read by one and all in academics and industry

link is ……http://orgspectroscopyint.blogspot.in/

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VILAZODONE SPECTRAL DATA

June 30, 2015 4:13 am / 1 Comment on VILAZODONE SPECTRAL DATA

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

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

ENJOY THE INTERPRETATIONS

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

Bin Hu , Qiao Song , and Yungen Xu *

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

http://pubs.acs.org/doi/full/10.1021/op300171m

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).

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

http://globalresearchonline.net/journalcontents/v29-1/35.pdf

file:///C:/Users/anthonyc/Downloads/lsyc_a_944268_sm4503.pdf

http://gxdxsrsp.cqvip.com/bitstream/123456789/13653/1/%E6%96%B0%E5%9E%8B%E6%8A%97%E6%8A%91%E9%83%81%E8%8D%AF%E7%BB%B4%E6%8B%89%E4%BD%90%E9%85%AE%E4%B8%AD%E9%97%B4%E4%BD%93%E7%9A%84%E5%90%88%E6%88%90%E5%B7%A5%E8%89%BA%E7%A0%94%E7%A9%B6

http://tuprints.ulb.tu-darmstadt.de/621/1/DissertationThiloMohrhardt.pdf

1H NMR PREDICT

13 C NMR PREDICT

will post a clear picture soon

…………………………

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 5HT_1A 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

“VIIBRYD (vilazodone hydrochloride) tablet VIIBRYD (vilazodone hydrochloride) kit [Forest Laboratories, Inc.]”. DailyMed. Forest Laboratories, Inc. December 2012. Retrieved28 October 2013.
“Clinical Data’s Vilazodone Patient Enrollment Over One Third Complete”. Business Wire. Berkshire Hathaway. 17 August 2006. Retrieved 12 April 2014.
“FDA approves Clinical Data Inc’s antidepressant”. Reuters. January 22, 2011.
“FDA approves Clinical Data Inc’s antidepressant”. Reuters. January 22, 2011. Retrieved 12 April 2014.
“Clinical Data, Inc. – Clinical Data, Inc. Submits New Drug Application for Vilazodone for the Treatment of Major Depressive Disorder”. Retrieved 12 April 2014.
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.
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

June 25, 2015 7:04 am / Leave a comment

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



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: 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)

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

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

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

Operating scheme

Operating scheme Instructions

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

Danger

27.8 g

H300 H314 EUH-

P264 P280 P305 + 351 + 338 P310

Reagents

Amount

Risk

Safety

Copper powder

Warning

30.5 g

H400 EUH-

P273

Solvents

Amount

Risk

Safety

tert-Butyl methyl ether

Danger

130 mL

H225 H315

P210

Petroleum ether (60-80)

Danger

300 mL

H225 H304 H315 H336 H411 EUH-

P210 P261 P273 P301 + 310 P331

Others

Amount

Risk

Safety

Sulfuric acid 2N

Danger

H314 H290 EUH-

P280 P301 + 330 + 331 P305 + 351 + 338 P309 + 310

Solvents for analysis

Amount

Risk

Safety

Petroleum ether (60-80)

Danger

H225 H304 H315 H336 H411 EUH-

P210 P261 P273 P301 + 310 P331

Acetic acid ethyl ester

Danger

H225 H319 H336 EUH066

P210 P261 P305 + 351 + 338

Dichloromethane

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			protective gas piping
	reflux condenser			heatable magnetic stirrer with magnetic stir bar
	rotary evaporator			suction filter
	suction flask			exsiccator with drying agent
	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

June 1, 2015 4:47 am / 1 Comment on (1S)-(-)-beta-Pinene

(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

MASS

RAMAN

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

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 :

RTECS :

DT5077000

HazardClass :

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

http://wikimapia.org/index_wjsl.php#lat=19.9433462&lon=75.2214387&z=18&m=b&ifr=1&permpoly=1608770

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)

May 21, 2015 8:15 am / Leave a comment

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

May 7, 2015 3:29 am / 1 Comment on 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:

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

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

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

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

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

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 …

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Omeprazole spectral visit

April 7, 2015 11:09 am / Leave a comment

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

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

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

HMBC

………………………………..

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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

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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.

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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

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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.

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