AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
Feb 092017
 

Abstract Image

 

tert-butyl(3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

STR1 STR2 STR3 str4

tert-Butyl (3aR,6aS)-5-Oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (1)

pure compound 1 (1.051 kg, 67%) as a white solid. Mp: 70–71 °C (uncorrected); [α]25D +0.40° (c 1.00 CHCl3); % purity: 98.5% (HPLC);
1H NMR (CDCl3, 400 MHz) δ: 1.46 (s, 9H), 2.15 (dd, J1 = 4.8 Hz, J2 = 19.6 Hz, 2H), 2.47 (dd, J1 = 7.4 Hz, J2 = 19.6 Hz, 2H), 2.93 (bs, 2H), 3.16–3.28 (m, 2H), 3.65–3.67 (m, 2H).;
13C NMR (CDCl3, 100 MHz) δ: 38.49, 39.36, 42.32, 50.51, 50.77, 79.49, 154.39, 217.65; IR (KBr): ν = 638, 771, 877, 1118, 1166, 1247, 1367, 1402, 1691, 1741, 2877, 2910, 2958, 2976, 3005 cm–1;
TOFMS: [C12H19NO3 + H+]: calculated 226.1438, found 152.0663 (M-OtBu)+ (100%), 170.0755 (M-tBu + H)+ (40%), 248.1166 (M + Na)+ (5%).
Anal. Calcd for C12H19NO3: C, 63.98; H, 8.50; N, 6.22. Found: C, 63.89; H, 8.27; N, 5.97.

HPLC conditions were as follows for compound ; Agilent 1100 series, column: YMC J’SPHERE C18 (150 mm X 4.6 mm) 4µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 210 nm, flow was set at 1.0 mL/min, and the temperature was 30 °C (Run time: 45 min). Gradient: 0 min, A = 90%, B = 10%; 5.0 min, A = 90%, B = 10%; 25 min, A = 0%, B = 100%; 30 min, A = 0%, B = 100%, 35 min, A = 90%, B = 10%; 45 min, A = 90%, B = 10%.

Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399

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Feb 092017
 

STR1

 

(3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine

STR1 STR2

Synthesis of (3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine (10)

off-white solid (53.9 kg, 68.3% yield). 1H NMR (400 MHz, DMSO-d6, δ): 1.20 (d, J = 6.8 Hz, 3 H), 2.52 (m, 1 H), 2.63 (s, 3 H), 3.21 (m, 1 H), 3.44 (m, 1 H), 3.58 (dd, J = 11.6, 3.1 Hz, 1 H), 3.72 (d, J = 11.5 Hz, 1 H), 3.92 (m, 3 H), 4.07 (d, J = 12.4 Hz, 1 H), 6.80 (s, 1 H); Assay (HPLC) 99%; Assay (QNMR) 100%; Chiral purity (HPLC) (R,R)-diastereoisomer 99.6%, (R,S)-diastereoisomer 0.4%.

 

Abstract Image

A Baeyer–Villiger monooxygenase enzyme has been used to manufacture a chiral sulfoxide drug intermediate on a kilogram scale. This paper describes the evolution of the biocatalytic manufacturing process from the initial enzyme screen, development of a kilo lab process, to further optimization for plant scale manufacture. Efficient gas–liquid mass transfer of oxygen is key to obtaining a high yield.

Development and Scale-up of a Biocatalytic Process To Form a Chiral Sulfoxide

The Departments of Pharmaceutical Sciences and Pharmaceutical Technology and Development, AstraZeneca, Silk Road Business Park, Macclesfield, Cheshire SK10 2NA, United Kingdom
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00391
Publication Date (Web): January 4, 2017
Copyright © 2017 American Chemical Society
*Tel: +44 (0)1625-519149. E-mail: william.goundry@astrazeneca.com.
Figure
Examples of biologically active molecules containing a sulfoxide or sulfoximine: esomeprazole (3), aprikalim (4), oxisurane (5), OPC-29030 (6), ZD3638 (7), buthionine sulfoximine (8), and AZD6738 (9).

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

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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Feb 092017
 

STR1 STR2 STR3

(±)-trans-ethyl 2-(3,4-difluorophenyl)Cyclopropanecarboxylate

C12H12F2O2

GC-MS (EI) m/z: [M]+ calc. for C12H12F2O2 + : 226.08; found: 226.08.

δH (400 MHz, CDCl3): 1.25 (1H, ddd, 3 J 8.4 Hz, 3 J 6.4 Hz, 2 J 4.5 Hz , 3-H); 1.28 (3H, t 3 J 6.4 Hz CH3Ethyl) 1.57-1.62 (2H, m, 3 J 9.2 Hz, 3 J 5.2 Hz, 2 J 4.5 Hz, 3-H + H2O), 1.84 (1H, ddd, 3 J 8.5 Hz, 3 J 5.3 Hz, 3 J 4.3 Hz , 2-H), 2.47 (1H, ddd, 3 J 9.5 Hz, 3 J 6.4 Hz, 3 J 4.2 Hz , 1-H), 4.17 (2H, q, 3 J 6.3 Hz, CH2Ethyl) 6.81-6.87 (1H, m, 3 J 8.5 Hz, 4 J 7.6 Hz, 4 J 2.4 Hz, 6-H’ ), 6.88 (1H, ddd, 3 J 11.5 Hz, 4 J 7.6 Hz, 4 J 2.2 Hz, 2-H’) 7.06 (1H, dt, 3 J 10.3 Hz, 3 J 8.2 Hz. 5-H’).

δc (400 MHz, CDCl3): 14.27 (CH3Ethyl), 16.84 (3-C) 24.04 (1-C), 25.14 (d, 4 J 1.4, 2-C), 60.71 (CH2Ethyl), 114.74 (d, 2 J 19 Hz, 2-C’), 117.09 (d, 2 J 18 Hz, 5-C’), 122.25 (dd, 3 J 6.1 Hz, 4 J 3.4 Hz, 6- C’), 137.06 (dd, 3 J 6.1 Hz, 4 J 3.4 Hz, 1- C’), 149.2 (dd, 1 J 248 Hz, 2 J 13 Hz, 4-C’) 151.32 (dd, 1 J 249 Hz, 2 J 12.5 Hz, 3-C’) 172.87 (Ccarbonyl).

[ ] 20 a D = -381.9 (c 1.0 in EtOH) for (1R,2R)-3, ee = 95%

Abstract Image

In this study a batch reactor process is compared to a flow chemistry approach for lipase-catalyzed resolution of the cyclopropanecarboxylate ester (±)-3. (1R,2R)-3 is a precursor of the amine (1R,2S)-2 which is a key building block of the API ticagrelor. For both flow and batch operation, the biocatalyst could be recycled several times, whereas in the case of the flow process the reaction time was significantly reduced.

Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor

School of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, United Kingdom
Chemessentia, SRL – Via G. Bovio, 6-28100 Novara, Italy
§ Institute of Process Research and Development, School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00346
Publication Date (Web): December 22, 2016
Copyright © 2016 American Chemical Society

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

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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Feb 042017
 

 

STR1

tert-Butyl 3a,4,7,7a-Tetrahydro-1H-isoindole-2(3H)-carboxylate

STR1 STR2 STR3 str4 str5

tert-Butyl 3a,4,7,7a-Tetrahydro-1H-isoindole-2(3H)-carboxylate 

 as a brown oil. % Purity: 93.72% (GC);
1H NMR (CDCl3, 400 MHz) δ: 1.47 (s, 9H), 1.89–194 (m, 2H), 2.20–2.33 (m, 4H), 3.08 (dd, J1 = 6.2 Hz, J2= 10.2 Hz, 1H), 3.17 (dd, J1 = 4.8 Hz, J2 = 10.4 Hz, 1H), 3.37–3.43 (m, 2H), 5.65 (s, 2H);
13C NMR (CDCl3, 100 MHz) δ: 24.63, 24.68, 28.49, 33.35, 34.23, 50.86, 50.92, 78.88, 124.19, 124.50, 155.22;
IR (CHCl3): ν = 756, 1128, 1170, 1217, 1411, 1685, 2937, 2978, 3009 cm–1;
TOFMS: [C13H21NO2 + H+]: calculated 224.1645, found 168.0958 (M-tBu + H)+ (100%), 246.1382 (M + Na)+ (5%).
GC conditions were as follows for compound 4; Agilent GC-FID 7890A, column: ZB-5MSi (30 m X 0.32 mm, 0.25 µm) with injector temperature 250 ºC and detector temperature 280 ºC, diluent was Methanol, Oven temperature was at 70 ºC isocratic for 3 min. then raised up to 250 ºC @ 20 ºC/min then 15 min. hold.
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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Feb 012017
 

 

STR1

2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid

STR1 STR2 STR3 str4 str5

2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid 

as a white solid. Mp: 162–163 °C, % purity: 94.09% (HPLC);
1H NMR (DMSO-d6, 400 MHz) δ: 1.38 (s, 9H), 2.10–2.18 (m, 2H), 2.28–2.32 (m, 2H), 2.49–2.50 (m, 2H, merged with DMSO peak), 2.97–3.03 (m, 2H), 3.33–3.40 (m, 2H), 12.23 (bs, 2H); 1H NMR (CD3OD, 400 MHz) δ: 1.46 (s, 9H), 2.26 (ddd, J1 = 2.8 Hz, J2 = 9.2 Hz, J3 = 16.0 Hz, 2H), 2.43 (dd, J1 = 5.2 Hz, J2 = 16.0 Hz, 2H), 2.69 (m, 2H), 3.16 (dd, J1 = 5.2 Hz, J2 = 10.8 Hz, 2H), 3.49–3.54 (m, 2H);
13C NMR (DMSO-d6, 100 MHz) δ: 28.49, 32.97, 36.49, 37.31, 50.10, 50.20, 78.67, 154.05, 173.96;
IR (KBr): ν = 871, 933, 1143, 1166, 1292, 1411, 1689, 1708, 2881, 2929, 2980, 3001 cm–1;
TOFMS: [C13H21NO6 – H+]: calculated 286.1296, found 286.1031(100%).
HPLC conditions were as follows for compound ; Agilent 1100 series, column: YMC J’SPHERE C18 (150 mm X 4.6 mm) 4µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 210 nm, flow was set at 1.0 mL/min, and the temperature was 30 °C (Run time: 45 min). Gradient: 0 min, A = 90%, B = 10%; 5.0 min, A = 90%, B = 10%; 25 min, A = 0%, B = 100%; 30 min, A = 0%, B = 100%, 35 min, A = 90%, B = 10%; 45 min, A = 90%, B = 10%.
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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Jan 312017
 

str5

Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)

STR1

IR (CHCl3): ν = 758, 1215, 1278, 1437, 1660, 1720, 2806, 2953, 3020, 3421 cm–1;

 

STR2

13C NMR (CDCl3, 100 MHz) δ: 51.53, 53.42, 58.37, 122.66, 127.28, 128.41, 128.55, 128.76, 138.24, 145.84, 166.58;

 

STR3

1H NMR (CDCl3, 400 MHz) δ: 3.23 (dd, J1 = 1.6 Hz, J2 = 6.0 Hz, 4H), 3.62 (s, 2H), 3.75 (s, 6H), 6.07 (dt, J1 = 1.6 Hz, J2 = 16.0 Hz, 2H), 6.97 (dt, J1 = 6.0 Hz, J2 = 16.0 Hz, 2H), 7.25–7.34 (m, 5H-merged with CDCl3 proton);

 

str4

TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).

str5

 

UPLC conditions were as follows for compound 11; Acquity Waters, column: BEH C18 (2.1 mm X 100 mm) 1.7 µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 220 nm, flow was set at 0.4 mL/min, and the temperature was 30 °C (Run time: 9 min). Gradient: 0 min, A = 90%, B = 10%; 0.5 min, A = 90%, B = 10%; 6.0 min, A = 0%, B = 100%; 7.5 min, A = 0%, B = 100%; 7.6 min, A = 90%, B = 10%; 9.0 min, A = 90%, B = 10%.

 

Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate) (11)

as a yellow oil. % purity: 93.4% (UPLC);
1H NMR (CDCl3, 400 MHz) δ: 3.23 (dd, J1 = 1.6 Hz, J2 = 6.0 Hz, 4H), 3.62 (s, 2H), 3.75 (s, 6H), 6.07 (dt, J1 = 1.6 Hz, J2 = 16.0 Hz, 2H), 6.97 (dt, J1 = 6.0 Hz, J2 = 16.0 Hz, 2H), 7.25–7.34 (m, 5H-merged with CDCl3 proton);
13C NMR (CDCl3, 100 MHz) δ: 51.53, 53.42, 58.37, 122.66, 127.28, 128.41, 128.55, 128.76, 138.24, 145.84, 166.58;
IR (CHCl3): ν = 758, 1215, 1278, 1437, 1660, 1720, 2806, 2953, 3020, 3421 cm–1;
TOFMS: [C17H21NO4 + H+]: calculated 304.1543, found 304.1703(100%).
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/acs.oprd.6b00399
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1-Bromo-4-fluoro-2-((2-iodobenzyl)oxy)benzene

 Uncategorized  Comments Off on 1-Bromo-4-fluoro-2-((2-iodobenzyl)oxy)benzene
Jan 252017
 

STR1

1-Bromo-4-fluoro-2-((2-iodobenzyl)oxy)benzene

CAS 1161931-51-6

STR1 STR2

Mp 89.8–92.3 °C.

IR (neat, ATR): 3072 (w), 1482 (s), 1451 (s), 1294 (s), 1294 (s) cm–1.

1H NMR (399 MHz, DMSO-d6) δ 5.12 (s, 2H), 6.81 (td, J = 8.49, 2.77 Hz, 1H), 7.14 (td, J = 7.64, 1.65 Hz, 1H), 7.18 (dd, J = 10.90, 2.82 Hz, 1H), 7.46 (td, J = 7.52, 0.92 Hz, 1H), 7.60 (dd, J = 7.64, 1.41 Hz, 1H), 7.62 (dd, J = 8.66, 6.23 Hz, 1H), 7.92 (dd, J = 7.83, 0.83 Hz, 1H).

13C NMR (100 MHz, DMSO-d6) δ 74.5, 99.2, 102.4 (d, J = 27.1 Hz), 105.8 (d, J = 3.4 Hz), 108.9 (d, J = 22.5 Hz), 128.5, 129.8, 130.3, 133.6 (d, J = 9.9 Hz), 138.0, 139.2, 155.4 (d, J = 10.7 Hz), 162.2 (d, J = 244.3 Hz).

GCMS: m/z [M]+ calcd for C13H9BrFIO: 405.88600; found: 405.88620.

1H AND 13C NMR PREDICT

STR1 STR2 STR3 str4

 

Org. Process Res. Dev., Article ASAP

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

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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Brc2ccc(F)cc2OCc1ccccc1I
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One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on One-Pot Reductive Cyclisations of Nitroanilines to Imidazoles
Jan 252017
 

Hana and co-workers ( Synlett 2010, 18, 2759−2764) from Genentech have developed a single-step procedure for conversion of 2-nitro aromatic amines to benzimidazoles. Addition of ammonium chloride proved necessary as Fe powder and formic acid alone was ineffective for nitro reduction. These conditions were compatible with a variety of functional groups on the aromatic, including boronate esters. The methodology was also extended to nitro aminopyridines but failed to deliver the desired product with isoxazole or pyrazole reactants.

Mild and General One-Pot Reduction and Cyclization of Aromatic and Heteroaromatic 2-Nitroamines to Bicyclic 2H-Imidazoles

Emily J. Hanan*, Bryan K. Chan, Anthony A. Estrada, Daniel G. Shore, Joseph P. Lyssikatos

*Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA, Email: hanan.emilygene.com

E. J. Hanan, B. K. Chan, A. A. Estrada, D. G. Shore, J. P. Lyssikatos, Synlett, 2010, 2759-2764.

DOI: 10.1055/s-0030-1259007


see article for more reactions

Abstract

A one-pot procedure for the conversion of aromatic and heteroaromatic 2-nitroamines into bicyclic 2H-benzimidazoles employs formic acid, iron powder, and NH4Cl as additive to reduce the nitro group and effect the imidazole cyclization with high-yielding conversions generally within one to two hours. The compatibility with a wide range of functional groups demonstrates the general utility of this procedure.


see article for more examples

//////////One-Pot, Reductive Cyclisations,  Nitroanilines,  Imidazoles

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

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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Telcagepant Revisited

 Uncategorized  Comments Off on Telcagepant Revisited
Jan 252017
 

Telcagepant structure.svg

Telcagepant, MK-0974

  • Molecular FormulaC26H27F5N6O3
  • Average mass566.523 Da
1-piperidinecarboxamide, N-[(3R,6S)-6-(2,3-difluorophenyl)hexahydro-2-oxo-1-(2,2,2-trifluoroethyl)-1H-azepin-3-yl]-4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]pyridin-1-yl)-
 CAS 781649-09-0

ChemSpider 2D Image | Telcagepant | C26H27F5N6O3

  • OriginatorMerck & Co
  • ClassAntimigraines; Piperidines
  • Mechanism of ActionCalcitonin gene-related peptide receptor antagonists

Migraine is a neurovascular disorder characterized by severe, debilitating, and throbbing unilateral headache. Though a leading cause of disability, it is a highly prevalent disease with a clear unmet medical need. With the significant progress achieved in the field of pathophysiology in the past decades, to date, it is well recognized that the neuropeptide calcitonin gene-related peptide (CGRP), which is expressed mainly in the central and peripheral nervous system, plays a crucial role in migraine. Antagonism of CGRP receptors, as a potential new therapy for the treatment of migraine, could offer the advantage of avoiding the cardiovascular liabilities associated with other existing antimigraine therapies.

Image result for Telcagepant

Telcagepant (INN) (code name MK-0974) is a calcitonin gene-related peptide receptor antagonist which was an investigational drug for the acute treatment and prevention of migraine, developed by Merck & Co. In the acute treatment of migraine, it was found to have equal potency to rizatriptan[1] and zolmitriptan[2] in two Phase III clinical trials. The company has now terminated development of the drug.

Mechanism of action

The calcitonin gene-related peptide (CGRP) is a strong vasodilator primarily found in nervous tissue. Since vasodilation in the brain is thought to be involved in the development of migraine and CGRP levels are increased during migraine attacks, this peptide may be an important target for potential new antimigraine drugs.

Telcagepant acts as a calcitonin gene-related peptide receptor (CRLR) antagonist and blocks this peptide. It is believed to constrict dilated blood vessels within the brain.[3]

Termination of a clinical trial

A Phase IIa clinical trial studying telcagepant for the prophylaxis of episodic migraine was stopped on March 26, 2009 after the “identification of two patients with significant elevations in serum transaminases”.[4] A memo to study locations stated that telcagepant had preliminarily been reported to increase the hepatic liver enzyme alanine transaminase (ALT) levels in “11 out of 660 randomized (double-blinded) study participants.” All study participants were told to stop taking the medication.[5]

On July 29, 2011, it was reported that Merck & Co. were discontinuing the clinical development program for telcagepant. According to Merck, “[t]he decision is based on an assessment of data across the clinical program, including findings from a recently completed six-month Phase III study”.[6]

CLIP

 

Image result for telcagepant

CLIP

Image result for telcagepant

Image result for telcagepant

 

CLIP

Asymmetric Synthesis of Telcagepant

http://pubs.acs.org/doi/abs/10.1021/jo101704b

Abstract Image

As part of the process of bringing a new API to market, it is often required to use an alternative synthetic strategy to the initial medicinal chemistry approach. Here Xu et al. of Merck Rahway disclose their efforts towards an improved multikilogram synthesis of telcagepant, a CGRP receptor antagonist for the treatment of migraines ( J. Org. Chem. 2010, 75, 7829−7841). The route described in the report is an example of a synthetic target driving the discovery of new chemistries.

Of note are the challenges they faced and overcame in particular the asymmetric Michael addition of nitromethane to a cinnamyl aldehyde. Initial attempts under Hayashi’s conditions gave promising results (50−75% yield) and moreover confirmed a high enantioselectivity could be achieved using the Jorgensen−Hayashi catalyst. However, the use of benzoic acid as the acidic cocatalyst gave rise to undesired byproducts. After performing a comprehensive screen of conditions Xu showed that the combination of the weak acids t-BuCO2H (5 mol %) and B(OH)3(50 mol %) minimized the level of impurities. Of specific note is that this is the first reported application of iminium organocatalysis on industrial scale.

The second milestone achieved in the strategy was the prevention of the protodefluorination under hydrogenative conditions. During the initial studies between 1.06−2.5% of the desfluoro compounds were formed by using Pd(OH)2/C in 100% conversion. To suppress the by product formation Xu screened a range of inorganic additives and found that 0.3 eq of LiCl gave a reproducible reaction where less than 0.2% of the desfluoro compounds were generated.
telcagepant as its crystalline potassium salt ethanol solvate in 92% yield with >99.9% purity and >99.9% ee.
1H NMR (400 MHz, d4-MeOH): δ 7.75 (dd, J = 5.3, 1.4 Hz, 1 H), 7.38 (dd, J = 7.6, 1.4 Hz, 1 H), 7.15 (m, 3 H), 6.70 (dd, J = 7.6, 5.3 Hz, 1 H), 4.85 (d, J = 11.4 Hz, 1 H), 4.55 (m, 1 H), 4.45 (dq, J = 15.4, 9.5 Hz, 1 H), 4.27 (m, 3 H), 4.05 (dq, J = 15.4, 9.0 Hz, 1 H), 3.61 (q, J = 7.1 Hz, 2 H), 3.46 (d, J = 15.4 Hz, 1 H), 3.16 (m, 1 H), 3.0 (m, 2 H), 2.42 (dq, J = 12.7, 4.4 Hz, 1 H), 2.27 (dq, J = 12.7, 4.4 Hz, 1 H), 2.16 (m, 3 H), 1.81 (m, 3 H). 1.18 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, d4-MeOH): δ 176.8, 166.1, 159.3, 157.4, 152.1 (dd, J = 246.8, 13.6 Hz), 149.4 (dd, J = 245.1, 13.1 Hz), 139.2, 134.7 (d, J = 11.9 Hz), 127.7, 126.3 (q, J = 279.7 Hz), 126.2 (dd, J = 7.1, 4.8 Hz), 124.3 (t, J = 3.4 Hz), 116.8 (d, J = 17.1 Hz), 114.5, 113.8, 58.5, 55.3, 55.2, 51.6, 49.9 (q, J = 33.6 Hz), 45.4, 45.3, 39.8, 35.9, 32.7, 30.74, 30.72, 18.5.
STR1 STR2

References

  1. Jump up^ Ho, Tw; Mannix, Lk; Fan, X; Assaid, C; Furtek, C; Jones, Cj; Lines, Cr; Rapoport, Am; Mk-0974, Protocol, 004, Study, Group (Apr 2008). “Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine”. Neurology. 70 (16): 1304–12. doi:10.1212/01.WNL.0000286940.29755.61. PMID 17914062.
  2. Jump up^ Ho TW, Ferrari MD, Dodick DW, et al. (December 2008). “Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial”. Lancet. 372 (9656): 2115–23. doi:10.1016/S0140-6736(08)61626-8. PMID 19036425.
  3. Jump up^ Molecule of the Month February 2009
  4. Jump up^ Clinical trial number NCT00797667 for “MK0974 for Migraine Prophylaxis in Patients With Episodic Migraine” at ClinicalTrials.gov
  5. Jump up^ Merck & Co.: Memo to all US study locations involved in protocol MK0974-049
  6. Jump up^ Merck Announces Second Quarter 2011 Financial Results
Telcagepant
Telcagepant structure.svg
Telcagepant-3D-balls.png
Clinical data
Routes of
administration
Oral
ATC code none
Legal status
Legal status
  • Development terminated
Pharmacokinetic data
Biological half-life 5–8 hours
Identifiers
CAS Number 781649-09-0 
PubChem (CID) 11319053
IUPHAR/BPS 703
ChemSpider 9494017 Yes
UNII D42O649ALL Yes
KEGG D09391 Yes
ChEMBL CHEMBL236593 Yes
Chemical and physical data
Formula C26H27F5N6O3
Molar mass 566.5283 g/mol
3D model (Jmol) Interactive image

1 to 10 of 14
Patent ID Patent Title Submitted Date Granted Date
US7534784 CGRP receptor antagonists 2008-11-13 2009-05-19
US7452903 CGRP receptor antagonists 2007-09-27 2008-11-18
US7235545 CGRP receptor antagonists 2005-11-17 2007-06-26
US6953790 CGRP receptor antagonists 2004-11-18 2005-10-11
Patent ID Patent Title Submitted Date Granted Date
US8394767 Methods of treating cancer using the calcitonin-gene related peptide (â??CGRPâ??) receptor antagonist CGRP8-37 2011-01-10 2013-03-12
US8080544 PRODRUGS OF CGRP RECEPTOR ANTAGONISTS 2010-11-25 2011-12-20
US7893052 CGRP RECEPTOR ANTAGONISTS 2010-11-25 2011-02-22
US2010286122 CGRP Antagonist Salt 2010-11-11
US7829699 Process for the Preparation of Cgrp Antagonist 2009-11-12 2010-11-09
US7772224 CGRP RECEPTOR ANTAGONISTS 2009-07-30 2010-08-10
US7745427 Cgrp Receptor Antagonists 2008-04-17 2010-06-29
US7718796 Process for the preparation of Caprolactam Cgrp Antagonist 2009-05-14 2010-05-18
US2010009967 SOLID DOSAGE FORMULATIONS OF TELCAGEPANT POTASSIUM 2010-01-14
US2009176986 Process for the Preparation of Pyridine Heterocycle Cgrp Antagonist Intermediate 2009-07-09

“ALL FOR DRUGS” CATERS TO EDUCATION GLOBALLY, No commercial exploits are done or advertisements added by me. This article is a compilation for educational purposes only.

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

///////////Telcagepant, MK-0974

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