Synthesis of 3H, 2H4, and 14C-MK 3814 (preladenant)

Article abstract of DOI:10.1002/jlcr.3490

MK 3814 is a potent and selective antagonist of the A_2a receptor. A_2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labelled forms of MK 3814 were synthesized. [³

Full text of DOI:10.1002/jlcr.3490

3
2
14
SYNTHESIS OF H, H AND C-MK 3814 (Preladenant)
4
D. Hesk, S. Borges, R. Dumpit, S. Hendershot, D. Koharski, P. McNamara, S. Ren, S.
Saluja, V. Truong and K. Voronin.
Labeled Compound Synthesis, Merck & Co., Inc., 126 E. Lincoln Avenue, RY 80R,
Rahway NJ 07065, USA.
Abstract
MK 3814 is a potent and selective antagonist of the A receptor. A receptor antagonists
2
a
2a
have the potential for the treatment of Parkinson’s disease. Three distinct isotopically labelled
3
forms of MK 3814 were synthesized. [ H]MK 3814 was prepared for a preliminary ADME
1
4
evaluation of the compound and [ C]MK 3814 for more definitive ADME work, including
2
an AME study in man. In addition [ H ]MK 3814 was prepared as an internal standard for a
4
LC-MS bioanalytical method. The paper discusses the synthesis of three isotopically labelled
forms of MK 3814.
Keywords: tritium exchange, ruthenium catalyst, deuterium, carbon-14
Introduction
Adenosine A antagonism has shown promise as a potential treatment for Parkinson’s
2
a
1
,2
disease, which is lacking treatments that control the long term progression of the disease.
During the course of our research efforts to discover novel A2a antagonists, MK 3814,
compound 1 was identified as a potent and selective antagonist of the A receptor with >
2
a
1
-4
1
,000 fold selectivity over the A , A and A receptors.
1 2b 3
In vivo, the compound was observed to display a robust oral anti-cataleptic activity in the rat
and additional clinical studies have demonstrated efficacy in the alleviation of Parkinson’s
1
,2
disease symptoms.
3
During lead optimization efforts, [ H]MK 3814 was prepared to obtain preliminary
absorption, distribution, metabolism and excretion data (ADME). Following the compound’s
2
advance into development, [ H ]MK 3814 was prepared for use as an internal standard
4
supporting analysis of bioanalytical samples obtained from toxicology and clinical studies.
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1002/jlcr.3490
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1
4
[
C]MK 3814 was subsequently prepared for conducting definitive ADME studies to support
1
4
compound registration, which also included a C absorption, metabolism and excretion
AME) study in man. Hence the paper will describe the synthesis of the three isotopomers of
(
MK 3814 prepared.
Results and Discussion
3
5
[
H]MK 3814 5 was prepared via Ru(Ph P) Cl catalyzed exchange of piperidine
3 3 2
intermediate 2 with 500 mCi, 50 Ci/mL tritiated water as shown in Figure 1.
3
Figure 1: Synthesis of [ H]MK 3814 (5)
This route had the advantage of utilizing readily available precursor compounds from the
6
3
Medicinal Chemistry synthesis and offered a route to a centrally located H label. Thus using
this chemistry, the methylene protons adjacent to the secondary piperazine nitrogen are
selectively exchanged. Hence 130 mCi of crude product 3 was isolated from the reaction,
purified by silica gel chromatography and coupled with tosylate 4 to generate 105 mCi of
3
crude [ H]MK 3814 5. A portion of the batch was purified by reverse phase HPLC to yield
2
1.5 mCi at radiochemical purity of >98% in systems 1 and 2 and a specific activity of 1.2
Ci/mmol.
3
H NMR analysis confirmed the tritium was exclusively incorporated alpha to the secondary
piperazine nitrogen in compound 3 with no evidence for incorporation alpha to the tertiary
piperazine nitrogen in compound 3, suggesting that formation of a Ru-N bond is required to
5
activate CH exchange and is consistent with previous results.
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2
The synthesis of [ H ]MK 3814 compound 10 is shown in Figure 2.
4
2
Figure 2: Synthesis of [ H ]MK 3814 (10)
4
2
[
H ]MK 3814 was prepared in three steps by adaption of the Medicinal Chemistry route as
4
6
2
described by Neustadt. Starting from commercially available [ H ]ethylene glycol 6, the
4
ditosyl intermediate 7 was prepared using standard conditions from p-tosyl chloride in 90%
yield. Intermediate 8 was then treated with sodium hydride in DMF followed by two
equivalents of 7 to generate compound 9 in 27% yield after precipitation from DMF and
water. Under these conditions, only minor amounts of the undesired N8 regioisomer are
generated. This material was then added to a DMF solution of compound 2 and heated at
8
5°C overnight to generate crude 10. Due to the low solubility of MK 3814 in common
organic solvents, chromatographic purification was not considered, hence the crude product
was initially purified with an ethanol: methanol slurry. This was followed by preparation of a
water soluble HCl salt with subsequent precipitation by addition of sodium hydroxide to
2
generate [ H ]MK 3814 at 97% purity using HPLC system 3.
4
1
4
6
For the synthesis of [ C]MK 3814, we initially examined the Medicinal Chemistry route as
shown in Figure 3:
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Figure 3: Medicinal Chemistry synthesis of MK 3814
Based on the results from exploratory metabolism studies conducted, users from the Drug
6
1
4
Metabolism group requested that the C be incorporated in the tricyclic core of the molecule.
This was based on the desire to trace the fate of the tricylic core should the ethylene bridge
connecting the phenylpiperazine be metabolically cleaved. Hence from the scheme, we
1
4
14
14
envisaged introduction of the C label via 2-[ C]furoic hydrazide, derived from
C
carbonylation of 2-furyllithium, which would achieve this objective. However to achieve this
1
4
via the route shown in figure 3, it would require carrying the C through six steps, with the
knowledge learned from the stable iostope synthesis that the final two steps proceed in very
1
4
modest yields. Starting with 2-amino-4,6-dichloropyrimidine-5-[ C]carbaldehyde would
1
4
still require the same number of steps, plus the additional steps to prepare the C starting
material. Hence we devised an alternative route, as shown in Figure 4, by utilizing an
7
,8
advanced intermediate available from the Process Chemistry route that had the side chain
14
14
already attached, still utilized 2-[ C]furoic acid and only required carrying the C label
through two steps.
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1
4
Figure 4: Synthesis of [ C]MK 3814 (14)
1
4
9
CO was prepared by the method of Dean and used to quench freshly prepared 2-
2
14
furyllithium and generate 2-[ C]furoic acid 11 in 48% yield. From preliminary experiments
conducted with CO , we initially observed that generated 2-[ C]furoic acid contained up to
3
1
3
13
2
1
2
12
0% C in the product from the presence of adventitious CO . Hence additional steps such
2
as using freshly distilled furan and THF, nitrogen bubbling of the furan solution prior to
addition of n-butyllithium and careful freeze thawing of the 2-furyllithium prior to addition of
1
4
14
CO were put into place and resulted in the preparation of 2-[ C]furoic acid at the specific
2
1
4
14
activity of the starting [ C]barium carbonate. This 2-[ C]furoic acid was then coupled to
hydrazide precursor 12 using standard EDC, HOBt conditions to generate compound 13 in
5
2% yield. Treatment of compound 13 with BSA at 120°C effected the desired cyclization
1
0
and Dimroth rearrangement to generate the desired product 14, which was obtained in 87%
14
yield after purification and 22% overall from [ C]barium carbonate. A total of 31.8 mCi at
radiochemical purities > 99% as determined by HPLC systems 4 and 5 with a specific
activity of 56.6 mCi/mmol was prepared.
Experimental
Materials
Tritiated water (50 Ci/mL) was purchased from Perkin Elmer life Sciences, Boston MA and
14
2
[
C]barium carbonate was purchased from Quotient Biosciences, Cardiff, UK. [ H ]Ethylene
4
glycol was purchased from CDN Isotopes, Pointe Claire, Canada. Compounds 2, 4 and 8
6
were obtained from MRL, Discovery Chemistry and Compound 12 and unlabelled MK 3814
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7
,8
were obtained from MRL, Process Chemistry. Tris-triphenylphosphine ruthenium (II)
chloride was purchased from Alfa. All remaining reagents were purchased from Aldrich or
2
14
Acros Organics and were used as received. All H and C steps were carried out under an
atmosphere of argon.
Liquid Scintillation Counting
Quantitation of radioactivity was performed using Packard 2200 or 2900 CA liquid
scintillation analyzers, with Scintiverse BD cocktail used throughout.
Thin Layer Chromatography
Thin layer chromatography was performed using Whatman LK6DF (Silica Gel 60) 5 x 20
cm, 0.25 mm plates. The plates were scanned on a Bioscan AR2000 linear analyzer. The
following systems were used:
1
2
3
) Methylene chloride: 2M methanolic ammonia (90:10)
) Methylene chloride: methanol (90:10)
) Methylene chloride: 7M methanolic ammonia (90:10)
High Performance Liquid Chromatography
A Waters 2695 ‘Alliance’ HPLC system was used. Chemical purity was determined using a
Waters 2996 photodiode array detector and radiochemical purity either using a Packard C150
radioflow detector with Packard FloScint III cocktail or a IN/US Beta Ram 2 radioflow
detector with IN/US InFlo 3 cocktail. The following systems were used:
1
2
) Phenomenex Gemini NX C18, 50 x 4.6 mm, 3 , 262 nm, 0.05 M pH 10
triethylammonium acetate (42: 58) methanol for 6 minutes followed by a step gradient
to methanol, 1 mL/min.
) Supelco Ascentis Express C18, 100 x 4.6 mm, 2.5 , 40°C, 262 nm, 0.1% aqueous
formic acid: 0.1% formic acid in acetonitrile. (95: 5 to 60: 40) linear gradient over 10
minutes followed by a step gradient to (5: 95), 3 minute hold, 1.8 mL/minute.
) YMC Basic 150 x 4.6 mm, 3 , 254 nm, 0.1% aqueous trifluoroacetic acid (77: 23)
acetonitrile, 1 mL/min.
3
4
) Develosil RP Aqueous, 150 x 3 mm, 5µ, 254 nm, 0.1% aqueous trifluoroacetic acid
(72: 28) 0.1% trifluoroacetic acid in acetonitrile for 15 minutes followed by a step
gradient to acetonitrile, 0.5 mL/minute.
5
) Phenomenex Gemini C18, 100 x 4.6 mm, 3µ, 254 nm, 0.05M pH 10 aqueous
triethylammonium acetate (65: 35) acetonitrile for 10 minutes followed by a step
gradient to acetonitrile, 1 mL/minute
Specific Activity measurements
14
The chemical concentration of [ C]MK 3814 were determined using a UV based HPLC
assay (System 4) using a reference standard of MK 3814. This data was used in conjunction
with the radiochemical concentration to calculate the specific activity values. Mass
3
spectrometry was used to determine the specific activity value for [ H]MK 3814.
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Mass Spectrometry
Mass Spectra were acquired on a JEOL MStation magnetic sector mass spectrometer
+
3
operating in the ESI or FAB+ ionization mode. LC/MS spectra for [ H]MK 3814 were
acquired on an Agilent LCS-MSD SL detector with a 1200 series chromatography system
+
operating in ES mode.
3
Synthesis of [ H]MK 3814 (5)
3
1
-(4-(2-methoxyethoxy)phenyl)[ H]piperazine 3
Compound 2 (24.5 mg) and tris-triphenylphosphine ruthenium (II) chloride (2.1 mg) were
weighed into a thick walled glass ampoule (6” h x 0.313” ID x 0.078” wall) and dioxane (100

l) was added. The ampoule was fitted with a rubber septum and tritiated water (50 Ci/ml,
00 mCi) was added via a syringe. The ampoule was frozen in liquid nitrogen, evacuated and
5
sealed in a flame, before being placed in an oil bath at 120 ºC for 3 hours. At the completion
of the reaction, the ampoule contents were partitioned between potassium hydroxide solution
(1M, 5 mL) and methylene chloride (5 mL). The methylene chloride layer was removed and
the aqueous layer extracted with methylene chloride (2 x 5 mL). The combined methylene
chloride extracts were washed with water and evaporated to dryness to yield 130.6 mCi of
crude compound 3 with a radiochemical purity of 80% (TLC system 1). The product was
purified on a 12 g Isco Gold column cartridge using a gradient of 0-20% 2M methanolic
ammonia in methylene chloride. A total of 105 mCi of 3 was isolated at a radiochemical
purity of 98% (TLC system 1), which was used directly in the next step.
3
2
-(furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)[ H]piperazin-1-yl)ethyl)-7H-
3
pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine [ H]MK 3814 (5)
In a 7 mL screw capped vial, compounds 3 (105 mCi) and 4 (44 mg, 0.102 mmol) were
dissolved in dimethylformamide (DMF) (500 L) and diisopropylethylamine (DIPEA) (36

L, 0.206 mmol) was added. The reaction was purged with argon and then was stirred
overnight at 70°C and analyzed by HPLC system 1 which showed 37% product formation
with an additional 49% of unreacted 3. The reaction was evaporated to dryness, dissolved in
dimethyl sulphoxide (7 mL) and a portion of the batch purified in a series of 200-500 µl
injections on a 10 x 250 mm Gemini NX C18 colunm with a mobile phase of 0.05M pH 10
triethylammonium acetate (42: 58) methanol at a flow rate of 5 mL/min, 262 nm. Fractions
containing the purified product were pooled, evaporated to dryness and dissolved in 120 mL
3
of methanol: ethanol: acetontrile (1:1:1). A total of 21.5 mCi of [ H]MK 3814 5 was
isolated at radiochemical purities of 98.2% and 98.9% (HPLC Systems 1 and 2), at a specific
activity of 1.2 Ci/mmol.
2
Synthesis of [ H ]MK 3814 (10)
4
2
[
H ]1,2-Ethanediol-1,2-bis(p-toluenesulphonate) 7
H ]Ethylene glycol (2 mL, 2.368 g, 39.3 mmol) 6 was dissolved in methylene chloride (50
4
4
2
[
mL) and triethylamine added (10 mL, 7.26 g, 71.7 mmol). The reaction was cooled to 0°C
and p-toluenesulphonyl chloride (11.5 g, 60.3 mmol) was added. The reaction was stirred for
three hours at this temperature before it was washed with water (3 x 50 mL) dried over
anhydrous sodium sulphate, filtered and evaporated to dryness. The crude product was
slurried in ethanol (5 mL) for 30 minutes, filtered and evaporated to dryness to yield 10.2 g of
7
, 90% which was used directly in the next step.
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2
-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-
2
yl)[ H ]ethyl p-toluenesulphonate 9
4
Compound 8 (2.5 g, 10.4 mmol) was dissolved in DMF (10 mL) and sodium hydride (60% in
mineral oil, 0.46 g, 11.5 mmol) was added. The resulting dark solution was stirred for 20
2
minutes after which [ H ]1,2-Ethanediol-1,2-bis(p-toluenesulfonate) (7.75 g, 20.7 mmol) 7
4
was added. The reaction was stirred overnight at room temperature and the resulting solid
was collected by filtration and washed with ethyl acetate (15 mL). The collected solid was
then suspended in DMF (20 mL) heated until fully dissolved and quickly filtered through a
pad of celite before water (5 mL) was added. The resulting precipitate was collected by
filtration, dried under vacuum to yield 1.23 g of 9 (27%) which was used directly in the next
step.
2
2
-(furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)[ H ]ethyl)-7H-
4
2
pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine [ H ]MK 3814 10
4
Compound 9 (1.23 g, 2.8 mmol) was suspended in DMF (25 mL) and heated to 85°C.
Compound 2 (1.33 g, 5.7 mmol) was added and the resulting clear brown solution stirred
overnight at 85°C at which point analysis in TLC system 1 showed complete reaction. The
reaction was cooled to room temperature, the solvent evaporated and the crude solid slurried
in a mixture of methanol (1:1) ethanol for four hours. The solid was collected by filtration,
2
and dried under vacuum for 4 hours to yield 860 mg of [ H ]MK 3814 10 at a purity as
4
determined by HPLC system 3 of 94%. The batch was then suspended in acetonitrile (7.8
mL) and water (7.8 mL), heated to 60°C and concentrated hydrochloric acid (37%, 152 µl)
was added which generated a clear yellow solution. Activated charcoal (80 mg) was added
and the suspension heated for 20 minutes at this temperature, before being filtered through a
pad of celite. The celite pad was washed with an additional 6 mL of acetonitrile (1:1) water
and the resulting solution cooled to room temperature. Sodium hydroxide solution (50%) was
added dropwise until a pH of 8.5 was achieved, at which point a white precipitate had been
generated. The solid was collected by filtration washed with water and dried overnight under
2
vaccum to yield 700 mg (50%) of [ H ]MK 3814 10. Chemical purity (area %) as determined
4
2
by HPLC system 3 was 99.3%. FAB+ MS: unlabelled MK 3814 m/z 504, [ H ]MK 3814 m/z
4
1
5
08. H NMR analysis: unlabelled MK 3814 signals at 3.8 ppm (m) and 4.4 ppm (m) were
1
2
absent in the H NMR spectrum of [ H ]MK 3814.
4
14
Synthesis of [ C]MK 3814 (14)
1
4
2
-[ C]Furoic acid (11)
Freshly distilled furan (3 mL) was dissolved in freshly distilled THF (50 mL) and cooled to -
0°C. The solution was bubbled with nitrogen for 20 minutes and n-butyllithium (2.5 M in
2
hexanes, 15 mL) was added. The reaction was stirred at -15°C for 40 minutes and sampled
for titration with diphenyl acetic acid which determined a 2-furyllithium concentration of
0
.58 M. The solution was capped and stored under nitrogen at -20°C.
14
In a flame dried heavy wall glass tube, [ C]barium carbonate (500 mg, 145 mCi, 2.5 mmol)
and lead (II) chloride (5.22 g, 18.7 mmol) were mixed and the tube attached to a vacuum line
and evacuated. A flame dried flask containing 2-furyllithium solution (0.58 M, 8.8 mL, 5.1
mmol) was attached to a second port on the vacuum line and subjected to two freeze thaw
14
cycles and then cooled to -78°C. The tube containing the, [ C]barium carbonate, lead (II)
chloride mixture was heated at 110°C under vaccum with an oil bath for 1 hour to dry the
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1
4
mixture. The mixture was then heated to 400°C with a Bunsen to generate CO which was
2
allowed to transfer to the flask containing 2-furyllithium. The reaction was stirred at -78°C
for 1 hour and then quenched by the addition of 5% sulphuric acid solution (5 mL). The
product was extracted with diethylether (5 x 10 mL), dried over anhydrous sodium sulphate,
filtered and evaporated to dryness. The crude product was dissolved in methylene chloride
and purified on a 40 g Isco Gold column using a gradient of 0-10% methanol in methylene
1
4
chloride. A total 70 mCi (48%) of 2-[ C]furoic acid 11 was isolated at a radiochemical purity
of 84% (TLC system 2) and used directly in the next step.
N'-(6-amino-1-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-1H-pyrazolo[3,4-
1
4
d]pyrimidin-4-yl)furan-2-[ C]carbohydrazide (13)
Compound 11 (70 mCi, 1.207 mmol) was dissolved in freshly distilled DMF (20 mL) and
Compound 12 (619 mg, 1.45 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)
(278 mg, 1.45 mmol), hydroxybenzotriazole (HOBt) (212 mg, 1.45 mmol) and DIPEA (0.63
mL, 3.62 mmol) were added. The reaction was stirred overnight at room temperature at
which point analysis in TLC System 3 showed product formation. The reaction was quenched
by the adddition of sodium bicarbonate solution (0.3 M, 40 mL) and extracted with
methylene chloride (100 mL and 3 x 40 mL). The combined methylene chloride extracts were
washed with water (5 mL), dried over anhydrous sodium sulphate, filtered and evaporated to
dryness. The crude product was purified on a 120 g Isco Gold column using a gradient of 0-
3
0% 7M methanolic ammonia in methylene chloride. A total of 36 mCi (51%) of purified 13
was isolated with a radiochemical purity of 97.7% as determined by TLC system 3.
1
4
2
-([ C]furan-2-yl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)ethyl)-7H-
1
4
pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine [ C]MK 3814 (14)
To a pressure tube containing compound 13 (36 mCi, 0.62 mmol) was added N,O-
bis(trimethylsilyl)acetamide (BSA) (12 mL, 49.1 mmol). The tube was flushed with nitrogen,
sealed and the resulting suspension stirred overnight at 120°C at which point analysis in
HPLC system 4 showed complete reaction. The reaction was quenched by the addition of 15
mL of water (1: 1) acetonitrile and the resulting precipitate was collected by centrifugation
and dried under vacuum. The solid was dissolved in a mixture of water (1: 1) acetonitrile:
HCl (37%, 0.38 mL) and the solution heated to 55°C for 30 minutes. Activated charcoal (65
mg) and celite (65 mg) were added and stirring was continued for a further 15 minutes at this
temperature before it was filtered through a pad of celite. The filtrate was evaporated to
dryness, dissolved in 12 mL of water (1: 1) acetonitrile and heated to 65°C. Sodium
hydroxide solution (50%) was added dropwise to pH 8.5 at which point a precipitate had
formed. The solid was collected by filtration, washed with water (2 x 5 mL) and dried under
1
4
vaccum to yield 277.4 mg, 31.8 mCi (87%) of [ C]MK 3814 (14). Radiochemical purity as
determined in HPLC systems 4 and 5 was 99.4% and 99.3% with a specific activity of 56.6
mCi/mmol.
Acknowledgements
The authors would like to thank Dr. T.M. Chan, Dr. Mary Senior, Dr. Rebecca Osterman and
Dr. Pradip Das for NMR and Mass spectrometry analysis.
References
1
) Bara-Himenez, W., Sherzai, A., Dimitrova, T., Favit, A., Bibbiani, F. Gillespie, M.,
Morris, M., Mouradian, M., Chase, T., Neurology, 2003, 61, 293.
2
) Hauser, R., Hubble, J., Chen, J., Morelli, M., Trends Neurosci., 2006, 29, 647
This article is protected by copyright. All rights reserved.

3
) Ongini, E., Dionosotti, S., Gessi, S., Irenius E., Fredholm, B., Naunyn Schmiederbegs
Arch. Pharmacol. 1999, 359, 7.
4
5
) Jacobson K., Ji, X., Drug Design Discov. 1999, 16, 217.
) Hesk, D., Borges, S., Hendershot, S., Koharski, D., McNamara, P., Ren, S., Saluja, S.,
Truong, V., Voronin, K., J. Lab. Comp. Radiopharm., 2016, 59, 190.
) Neustadt, B., Hao, J., Lindo, N., Greenlee W., Stamford A., Tulshian, D., Ongini, E.,
Hunter, J., Monopoli, A., Bertorelli, R., Foster, C., Arik, L., Lachowicz, J., Ng, K., Feng,
K., Biorg. Med. Chem. Lett., 2007, 17, 1376.
6
7
) Kuo, S., Tsai, D., Tran, J., Zhang, P., Jones, A., U.S. Pat. Appl. Publ. 2005,
US20050090492 A1:20050428.
8
9
1
) Kuo, S., Tran, L.T., Zhang, P., PCT Int. Appl. 2005, WO 20050542245 A2: 2050616.
) Dean, D., Wallace, M., Marks, T, Melillo, D, Tetrahedon Lett., 1997, 38, 919.
0) Snyder N., Adams, T., ‘Name Reactions in Heterocyclic Chemistry (II)’. Li. J (Ed) 2011,
5
54.
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2
14
SYNTHESIS OF H, H AND C-MK 3814 (Preladenant)
4
D. Hesk, S. Borges, R. Dumpit, S. Hendershot, D. Koharski, P. McNamara, S. Ren, S.
Saluja, V. Truong and K. Voronin.
MK 3814
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