AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER
Mar 142017
 
Dimethylcarbamoylchlorid Strukturformel.svg
Identifiers
79-44-7
ECHA InfoCard 100.001.099
PubChem 6598
Properties
C3H6ClNO

Dimethylcarbamoyl Chloride

Figure

Mechanisms for the Formation of Dimethylcarbamoyl Chloride

Thionyl chloride is the most common reagent in process chemistry for the conversion of a carboxylic acid to an acid chloride. One of the primary factors is cost, since the reagent is inexpensive and represents one of the most cost-efficient ways of preparing acid chlorides. However, one disadvantage of thionyl chloride is the potential formation of dimethylcarbamoyl chloride, a known carcinogen in animal models, when used in combination with DMF as catalyst.

Dimethylcarbamoyl chloride is a reagent for transferring a dimethylcarbonyl group to alcoholic or phenolic hydroxyl groups forming dimethyl carbamates, usually having pharmacological or pesticidal activities. Because of its high toxicity and its carcinogenic properties shown in animal experiments and presumably also in humans,[1] dimethylcarbamoyl chloride can only be used under stringent safety precautions.

Production and occurrence

The production of dimethylcarbamoyl chloride from phosgene and dimethylamine (DMA) was reported as early as 1879 (reported as “Dimethylharnstoffchlorid” – dimethylurea chloride).[2]

Synthese von Dimethylcarbamoylchlorid (DMCC) mit Dimethylamin

Dimethylcarbamoyl chloride can be produced in high yields (90%) at 275 °C by reacting phosgene with gaseous dimethylamine in a flow reactor.[3] To suppress the formation of ureas excessive phosgene is used (in a 3:1 ratio).

The reaction can also be carried out at the laboratory scale with diphosgene or triphosgene and a aqueous dimethylamine solution in the two-phase system benzene+xylene/water in a stirred reactor with sodium hydroxide as an acid scavenger. However, considerably lower yields (56%) are achieved due to the hydrolysis sensitivity of dimethylcarbamoyl chloride .[4]

Dimethylcarbamoyl chloride is also formed (together with methyl chloride) when reacting phosgene with trimethylamine.[5]

Synthese von Dimethylcarbamoylchlorid (DMCC) mit Trimethylamin

A more recent process is based on dimethylamine chloride, which is converted practically quantitatively to dimethylcarbamoyl chloride on a palladium catalyst under pressure with carbon monoxide at room temperature.[6]

Synthese von Dimethylcarbamoylchlorid (DMCC) aus Chloramin

Dicarbamoyl chloride can also be formed in small amounts (0-20 ppm) from dimethylformamide (DMF) in the Vilsmeier-Haack reaction[7] or when DMF is used as a catalyst in the reaction of carboxylic acids with thionyl chloride to the corresponding carboxylic acid chlorides.[8]

Synthese von Dimethylcarbamoylchlorid (DMCC) mit Dimethylformamid (DMF)

The tendency towards dicarbamoyl chloride formation depends on the chlorination reagent (thionyl chloride> oxalyl chloride> phosphorus oxychloride) and is higher in the presence of a base. However, dicarbamoyl chloride hydrolyses very quickly to dimethylamine, hydrochloric acid and carbon dioxide (with a half-life of about 6 minutes at 0 °C) so that less than 3 ppm of dicarbamoyl chloride are found in the Vilsmeier product after aqueous work-up.[9]

Properties[edit]

Dimethylcarbamoyl chloride is a clear, colorless, corrosive and flammable liquid with a pungent odor and a tear-penetrating effect, which decomposes rapidly in water.[10]Because of its unpleasant, toxic, mutagenic and carcinogenic properties[11][12] it has to be used under extreme precautions.

Dimethylcarbamoyl chloride behaves like an acid chloride whose chlorine atom can be exchanged for other nucleophiles. Therefore, it reacts with alcohols, phenols and oximes to the corresponding N, N-dimethylcarbamates, with thiols to thiolourethanes, with amines and hydroxylamine to substituted ureas, and with imidazoles and triazoles to carbamoylazoles.[13]

Reaktionen von Dimethylcarbamoylchlorid (DMCC) mit Nukleophilen

Dimethylcarbamoyl chloride is less reactive and less selective to substrates with multiple nucleophilic centers than conventional acid chlorides.

Unsaturated conjugated aldehydes such as (2E)-butenal react with dimethylcarbamoyl chloride forming dienyl carbamates, which can be used as dienes in Diels-Alder reactions.[14]

Synthese von Dienylcarbamaten mit Dimethylcarbamoylchlorid (DMCC)

Alkali metal carboxylates react with dimethylcarbamoyl chloride forming the corresponding dimethylamides. Dimethylcarbamoyl chloride reacts with anhydrous sodium carbonate[15] or with excess dimethylamine to tetramethylurea.[16]

The reaction of dimethylcarbamoyl chloride with DMF forms tetramethylformamidinium[17] chloride which is a major intermediate in the preparation of tris(dimethylamino)methane, a reagent for the introduction of enamine functions in conjunction with activated methylene groups[18] and the preparation of amidines.[19]

Synthese von Tris(dimethylamino)methan mit Diemthylcarbamoylchlorid (DMCC)

Dimethylcarbamoyl chloride is a starting material for the insecticide class of the dimethyl carbamates[20] which act as inhibitors of acetylcholinesterase, including dimetilane,[21]and the related compounds isolane, pirimicarb and triazamate.

Synthesis of Dimetilan mit Dimethylcarbamoylchlorid

The quaternary ammonium compounds neostigmine[22] finds pharmaceutical applications as acetylcholinesterase inhibitors. It is obtained from 3-dimethylaminophenol and dimethylcarbamoyl chloride and subsequent quaternization with methyl bromide or dimethyl sulfate[23]

Synthese von Neostigmin mit Dimethylcarbamoylchlorid

and pyridostigmine, which is obtainable from 3-hydroxypyridine and dimethylcarbamoyl chloride and subsequent reaction with methyl bromide.[24]

Synthese von Pyridostigmin mit dimethylcarbamoylchlorid

Dimethylcarbamoyl chloride is also used in the synthesis of the benzodiazepine camazepam.[25]

Synthese von Camazepam mit Dimethylcarbamoylchlorid

Image result for Dimethylcarbamoyl Chloride

13c NMR

MASS

RAMAN

References

  1. Jump up^ R.P. Pohanish (2011) (in German), Sittig’s Handbook of Toxic and Hazardous Chemicals and Carcinogens, 6th Edition, Amsterdam: Elsevier, pp. 1045–1047, ISBN 978-1437778694
  2. Jump up^ W. Michler; C. Escherich (1879), “Ueber mehrfach substituirte Harnstoffe” (in German), Ber. Dtsch. Chem. Ges. 12 (1): pp. 1162–1164, doi:10.1002/cber.187901201303
  3. Jump up^ R.J. Slocombe; E.A. Hardy; J.H. Saunders; R.L. Jenkins (1950), “Phosgene derivatives. The preparation of isocyanates, carbamyl chlorides and cyanuric acid” (in German), J. Am. Chem. Soc. 72 (5): pp. 1888–1891, doi:10.1002/ja01161a009
  4. Jump up^ G. Karimipour; S. Kowkabi; A. Naghiha (2015), “New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity” (in German), Braz. Arch. Biol. Technol. 58 (3), doi:10.1590/S1516-891320500024
  5. Jump up^ H. Babad; A.G. Zeiler (1973), “Chemistry of Phosgene” (in German), Chem. Rev. 73 (1): pp. 75–91, doi:10.1021/cr60281a005
  6. Jump up^ T. Saegusa; T. Tsuda; Y. Isegawa (1971), “Carbamoyl chloride formation from chloramine and carbon monoxide” (in German), J. Org. Chem. 36 (6): pp. 858–860, doi:10.1021/jo00805a033
  7. Jump up^ M. Stare; K. Laniewski; A. Westermark; M. Sjögren; W. Tian (2009), “Investigation on the formation and hydrolysis of N,N-dimethylcarbamoyl chloride (DMCC) in Vilsmeier reactions using /GC/MS as the analytical detection method” (in German), Org. Process Res. Dev. 13 (5): pp. 857–862, doi:10.1021/op900018f
  8. Jump up^ D. Levin (1997), “Potential toxicological concerns associated with carboxylic acid chlorination and other reactions” (in German), Org. Process Res. Dev. 1 (2): pp. 182, doi:10.1021/op970206t
  9. Jump up^ A. Queen (1967), “Kinetics of the hydrolysis of acyl chlorides in pure water” (in German), Canad. J. Chem. 45 (14): pp. 1619–1629, doi:10.1139/v67-264
  10. Jump up^ C.B. Kreutzberger; R.A. Olofson (2001), “Dimethylcarbamoyl Chloride” (in German), e-EROS Encyclopedia of Reagents for Organic Synthesis, doi:10.1002/047084289X.rd319
  11. Jump up^ P. Jäger; C.N. Rentzea; H. Kieczka (2014) (in German), Carbamates and Carbamoyl Chloride, in Ullmann’s Fine Chemicals, Weinheim: Wiley-VCH, pp. 57–58, ISBN 978-3-527-33477-3
  12. Jump up^ “Dimethylcarbamoyl Chloride, CAS No. 79-44-7” (PDF). Report on Carcinogens, Thirteenth Edition (in German). National Toxicology Program, Department of Health and Human Services. Retrieved 2016-09-25.
  13. Jump up^ C.B. Kreutzberger, R.A. Olofson (2007-02-01). “Dimethylcarbamoyl Chloride” (in German). John Wiley&Sons, Ltd. Retrieved 2016-09-27.
  14. Jump up^ P.F. De Cusati; R.A. Olofson (1990), “A simple synthesis of 1-(1,3-butadienyl)carbonates and carbamates” (in German), Tetrahedron Lett. 31 (10): pp. 1405–1408, doi:10.1016/S0040-4039(00)88817-6
  15. Jump up^ J.K. Lawson Jr.; J.A.T. Croom (1963), “Dimethylamides from alkali carboxylates and dimethylcarbamoyl chloride” (in German), J. Org. Chem. 28 (1): pp. 232–235, doi:10.1021/jo1036a513
  16. Jump up^ US 3597478, M.L. Weakly, “Preparation of tetramethylurea”
  17. Jump up^ Z. Arnold (1959), “The preparation of tetramethylformamidinium salts and their vinylogues” (in German), Coll. Czech. Chem. Commun. 24: pp. 760–765, doi:10.1135/cccc19590760
  18. Jump up^ H. Meerwein; W. Florian; N. Schön; G. Stopp (1961), “Über Säureamidacetale, Harnstoffacetale und Lactamacetale” (in German), Justus Liebigs Ann. Chem. 641 (1): pp. 1–39, doi:10.1002/jlac.19616410102
  19. Jump up^ H. Bredereck; F. Effenberger; Th. Brendle (1966), “Synthese und Reaktionen von Trisdimethylaminomethan” (in German), Angew. Chem. 78 (2): pp. 147–148, doi:10.1002/ange.19660780212
  20. Jump up^ “Compendium of Pesticide Common Names” (in German). Alan Wood. Retrieved 2016-09-27.
  21. Jump up^ US 3452043, T. Grauer, H. Urwyler, “Production of 1-N,N-dimethylcarbamoyl-5-methyl-3-N,N-dimethyl-carbamoyl-oxy-pyrazole”
  22. Jump up^ J.A. Aeschlimann; M. Reinert (1931), “Pharmacological action of some analogues of physostigmine” (in German), J. Pharmacol. Exp. Ther. 43 (3): pp. 413–444
  23. Jump up^ US 1905990, J.A. Aeschlimann, “Disubstituted carbamic acid esters of phenols containing a basic constituent”
  24. Jump up^ US 2572579, “Disubstituted carbamic acid esters of 3-hydroxy-1-alkyl-pyridinium salts”
  25. Jump up^ DOS 2448015, “Verfahren zur Herstellung des 3-N,N-Dimethylcarbamoyl-oxy-1-methyl-5-phenyl-7-chlor-1,3-dihydro-2H-1,4-benzodiazepin-2-on”

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Mar 132017
 

Cholecystokinin-2/gastrin antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anti-inflammatory analgesics for the treatment of inflammatory bowel disease

Med. Chem. Commun., 2017, Advance Article
DOI: 10.1039/C6MD00707D, Research Article
E. Lattmann, J. Sattayasai, R. Narayanan, N. Ngoc, D. Burrell, P. N. Balaram, T. Palizdar, P. Lattmann
Arylated 5-hydroxy-pyrrol-2-ones were prepared in 2 synthetic steps from mucochloric acid and optimised as CCK2-selective ligands using a range of assays.

Cholecystokinin-2/gastrin antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anti-inflammatory analgesics for the treatment of inflammatory bowel disease

*Corresponding authors
aSchool of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
E-mail: e.lattmann@aston.ac.uk
bDepartment of Pharmacology, Faculty of Medicine, Khon Kaen University, 40002 Khon Kaen, Thailand
cDepartment of Medicine, University of Tennessee Health Science Center, Memphis, USA
dPNB Vesper Life Science PVT, Cochin, India
Med. Chem. Commun., 2017, Advance Article

DOI: 10.1039/C6MD00707D

Arylated 5-hydroxy-pyrrol-2-ones were prepared in 2 synthetic steps from mucochloric acid and optimised as CCK2-selective ligands using radiolabelled binding assays. CCK antagonism was confirmed for the ligands in isolated tissue preparations. DSS (dextran sulfate sodium)-induced inflammation was analysed for derivative 7 and PNB-001 with L-365,260 as a standard. The IC50 of PNB-001 was determined to be 10 nM. Subsequent in vivo evaluation confirmed anti-inflammatory activity with respect to IBD assays. The best molecule, PNB-001, showed analgesic activity in the formalin test and in the hotplate assay, in which the analgesic effect of 1.5 mg kg−1 PNB-001 was equivalent to 40 mg kg−1 tramadol. The CCK2-selective antagonist PNB-001 protected rats against indomethacin-induced ulceration at similar doses. The GI protection activity was found to be more potent than that of the 10 mg kg−1 dose of prednisolone, which served as a standard.

General Method: The relevant amine (2.5 times excess) was added to a solution of lactone A – E (0.7 mol) in ether (10 ml) and stirred on ice for 30 minutes, allowing to warm up to RT over the time. The resultant mixture was poured into 5 ml water and separated by separating funnel. The mixture was washed with water three times. The organic layer was dried over magnesium sulphate and the solvent was removed under vacuum. All compounds gave an oily solid which were passed through a column (80% ether, 20% petrol ether). The resulting fractions were dried from excess solvent under vacuum to yield crystals. 4-Chloro-1-cyclopropyl-5-hydroxy-5-phenyl-1,5-dihydro-pyrrol-2-one 1 Yield = 83 %; mp: 177-179 oC;
MS (APCI(+)): 193/195 (M+1), 250/252 (M+) m/z
1H NMR (CDCl3) 250 MHz:  = 7.41 (m, 5H), 6.09 (s, 1H), 3.50 (m, 1H), 2.18 (m, 1H), 0.95-1.04 & 0.38-0.69 (m, 4H);
13C NMR (CDCl3) 167.4, 154.8, 135.2, 129.2, 128.8, 126.1, 122.2, 93.5, 22.6 , 3.8, 5.1;
IR (KBr-disc)  max: 3416, 3260, 3105, 3011, 2363, 2338, 1671, 1602, 1490, 1450, 1409, 1369, 1256, 1144, 1032, 939, 833, 752, 702 cm-1 .
/////////////////Cholecystokinin-2/gastrin antagonists, 5-hydroxy-5-aryl-pyrrol-2-ones,  anti-inflammatory analgesics, inflammatory bowel disease
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tert-butyl(3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

 Uncategorized  Comments Off on tert-butyl(3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate
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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(3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine

 spectroscopy  Comments Off on (3R)-4-[2-chloro-6-[[(R)-methylsulfinyl]methyl]pyrimidin-4-yl]-3-methyl-morpholine
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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(±)-trans-ethyl 2-(3,4-difluorophenyl)Cyclopropanecarboxylate

 spectroscopy  Comments Off on (±)-trans-ethyl 2-(3,4-difluorophenyl)Cyclopropanecarboxylate
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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tert-Butyl 3a,4,7,7a-Tetrahydro-1H-isoindole-2(3H)-carboxylate

 Uncategorized  Comments Off on tert-Butyl 3a,4,7,7a-Tetrahydro-1H-isoindole-2(3H)-carboxylate
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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2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on 2,2′-(1-(tert-Butoxycarbonyl)pyrrolidine-3,4-diyl)diacetic Acid
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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Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)

 spectroscopy, SYNTHESIS, Uncategorized  Comments Off on Dimethyl 4,4′-(Benzylazanediyl)(2E,2′E)-bis(but-2-enoate)
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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