Scalable Synthesis of Trifluoromethylated Imidazo-Fused N-Heterocycles Using TFAA and Trifluoroacetamide as CF3-Reagents

Article abstract of DOI:10.1021/acs.orglett.7b03291

A scalable synthesis of trifluoromethylated imidazo-fused N-heterocyles from heterocyclic benzylamines using TFAA as trifluoromethylating reagent is presented. The reaction proceeds via intermediate benzylic N-trifluoroacetamides followed by dehydrative cyclization to the products. To further broaden the scope and practicality, a new method for the preparation of benzylic N-trifluoroacetamides via alkylation of trifluoroacetamide with benzyl (pseudo)halides was developed. Both methods proceed under mild conditions, and their symbiosis provides access to a wide range of novel CF₃-heterocycles.

Full text of DOI:10.1021/acs.orglett.7b03291

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Scalable Synthesis of Trifluoromethylated Imidazo-Fused
N‑Heterocycles Using TFAA and Trifluoroacetamide as CF3‑Reagents
Gabriel Schafer,* Muhamed Ahmetovic, and Stefan Abele
̈
Process Chemistry R&D, Idorsia Pharmaceuticals Ltd., Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland
S
* Supporting Information
ABSTRACT: A scalable synthesis of trifluoromethylated imidazo-fused N-heterocyles from heterocyclic benzylamines using
TFAA as trifluoromethylating reagent is presented. The reaction proceeds via intermediate benzylic N-trifluoroacetamides
followed by dehydrative cyclization to the products. To further broaden the scope and practicality, a new method for the
preparation of benzylic N-trifluoroacetamides via alkylation of trifluoroacetamide with benzyl (pseudo)halides was developed.
Both methods proceed under mild conditions, and their symbiosis provides access to a wide range of novel CF3-heterocycles.
chemistry.11 In this paper, we disclose the facile synthesis of
he development of new methodologies for the introduction
Tof fluorine into small organic compounds has become a trifluoromethylated N-heterocycles from heterocyclic benzyl-
amines using TFAA as an inexpensive CF3-source and
dehydrating agent. The reaction is operationally simple, shows
a high functional group tolerance, and is robust on at least a 150 g
scale.
For a recent campaign, we needed to rapidly produce 100 g of
6-(trifluoromethyl)imidazo[1,5-a]pyrimidine (3). We envi-
sioned its synthesis from commercially available pyrimidin-2-
ylmethanamine HCl (1) and TFAA via in situ formation of the
corresponding trifluoroacetamide 2 followed by dehydrative
cyclization (Scheme 1). For screening purposes, we prepared N-
major research interest in academic and industrial chemistry
laboratories over the last two decades.1 This rapid expansion of
fluorination reactions can be attributed to the beneficial effects
that fluorine and fluorine-containing groups exert in pharma-
ceuticals and agrochemicals: fluorinated compounds often show
increased metabolic stabilities and improved pharmacokinetic
properties compared to their nonfluorinated analogs.2 Among
the above-mentioned fluorine-containing groups, the trifluoro-
methyl (CF3) group is the front-runner and received the most
attention by the organic synthetic community.3 Different
approaches for the trifluoromethylation of arenes and hetero-
arenes have been disclosed, using radical,4 nucleophilic,5 or
electrophilic6 trifluoromethylating reagents. From a process
chemist’s point of view, most of these reagents are impractical to
use on scale7 due to their high price,8 their poor atom economy,
or general safety concerns.9 Therefore, many CF3-containing
arenes are still prepared by radical chlorination of aryl methyl
groups followed by high-pressure or high-temperature treatment
with HF or SbF3/SbF5.10 These approaches may work well for
simple arenes, but the functional-group tolerance under these
harsh conditions is, not surprisingly, very low. Therefore,
alternative protocols that proceed under mild conditions using
inexpensive CF3-sources are still an urgent synthetic need.
Inexpensive and atom-efficient CF3-sources are trifluoroacetic
acid (TFA) and its anhydride (TFAA). TFAA is available on
metric ton-scale for $35/kg.11 The use of TFAA in trifluor-
omethylation reactions has been scarce. Recently, Stephenson et
al. described an elegant radical trifluoromethylation of arenes and
heteroarenes using TFAA as the trifluoromethylating reagent,
underlining the great potential of this reagent in the aspect of CF3
Scheme 1. Dehydrative Cyclization of Trifluoroacetamide (2)
into Imidazo-Fused Pyrimidine (3)
trifluoroacetamide 2 separately and tested different bases for its
conversion into the desired product. Several bases (Cs2CO3,
DBU, or KOtBu) left the starting material unreacted when
treated with a slight excess of TFAA. Onthe other hand, the use of
triethylamine or sodium hydride (NaH) resulted in full
conversion of trifluoroacetamide (2) and clean formation of
the product (3). For safety and handling reasons,12 triethylamine
(NEt3) was our base of choice.
Received: October 23, 2017
© XXXX American Chemical Society
A
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Letter
Increasing the amounts of triethylamine and TFAA allowed for
the direct preparation of the desired product (3) from pyrimidin-
2-ylmethanamine HCl (1) in 76% yield on 500 mg scale
(purification by FC). With regard to scale-up, the high solubility
of product 3 in a wide range of classical anti-solvents (e.g., methyl
tert-butyl ether, isopropyl alcohol, ambient H2O) made its
isolation via crystallization very challenging.13 In addition, we
observed oiling out of the low-melting product (mp 99 °C) from
nonpolar solvents such as heptane. Thanks to intensive process
optimization efforts, we found that after aqueous basic quench of
the reaction mixture and removal of THF by distillation the
trifluoromethylated product would nicely crystallize at 5−10 °C
as yellow, glimmery solid from the aqueous solution. Washing of
the cake with cold H2O followed by drying at 65 °C under
reduced pressure provided the desired product in decent yield
(110 g, 57%) and excellent purity (>99% a/a, 99% w/w)14 on 150
g scale (Scheme 2). We anticipate that further process
heterocycles derived from pyrazine (16), pyridazine (17),
thiazole (18), and benzothiazole (19) were synthesized and
isolated inmoderate to good yield (Scheme 3, B). In certain cases,
overacylated heterocyclic products were obtained (20−22). For
these highly activated substrates, the use of lower amounts of
TFAA did not lead to clean formation of the nonacylated
imidazo-fused heterocycles.18 By switching from TFFA to
commercially available difluoroacetic anhydride ($1200/kg),19
the corresponding difluoromethylated pyrimidine 15 was
synthesized on 10 g scale, and isolated in good yield and
excellent purity. Such difluoromethylated imidazo-fused pyr-
imidines (and pyridines) are completely unknown, and could
serve as exciting new building blocks in medicinal chemistry and
agrochemical laboratories.20
The benzylamine starting materials used so far were
commercially available, and the majority of them prepared via
reduction of the parent aryl nitrile. Even though this sequence is
routinely used, it precludes certain functional groups to be
present in the benzylamines (e.g., CN, NO2), and often multistep
sequences are necessary to prepare such compounds. In order to
circumvent the short-comings of aryl nitrile reduction and to
increase the scope and practicality of our novel method, we were
eager to find an alternative way to access N-trifluoroacetamides
such as 24a from commercially available trifluoroacetamide and
heterocyclic benzyl tosylates or halides (23). These starting
materials are conveniently accessed via halogenation or tosylation
of benzyl alcohols, or, in the latter case, also via radical
halogenation of 2-picoline derivatives. To our surprise, a Reaxys
search delivered only a handful of examples that described the
direct benzylation of trifluoroacetamide with benzyl bromides,
most of them using sodium hydride as a base. No examples with
benzyl tosylates could be found.
Using 6-(bromomethyl)nicotinonitrile (23a) as model sub-
strate, we explored its trifluoroacetamidation testing different
bases and solvents. After extensive screening, we found that
cesium carbonate in THF performed best (Scheme 4, step 1). An
excess of trifluoroacetamide (1.7 equiv) had to be used in order to
minimize competing overalkylation of product 24a (see the
Supporting Information for further information). These novel
conditions allowed for the synthesis of heterocyclic benzylic N-
trifluoroacetamides bearing a nitrile (24a), ester (24b), iodo
(24c), nitro (24i), or unprotected benzyl alcohol (24j) moiety
(Scheme 4, step 1). The majority of these products would be hard
or impossible to obtain via a nitrile reduction/acylation strategy,
as the attached functional groups are very prone to hydrolytic
reduction/cleavage. The reaction also worked when secondary
Scheme 2. Synthesis of 3 from 1 on a 150 g Scale
optimizations of the crystallization procedure (volumes,15 cake
washings, etc.) will increase the yield of isolated product and
minimize product loss into the mother liquor.
We were curious if our optimized conditions were also viable to
access other trifluoromethylated imidazo-fused N-heterocycles.16
To our delight, a wide range of trifluoromethylated imidazo[1,5-
a]pyridines could be synthesized (Scheme 3, A). Our conditions
allowed for the conversion of electron-rich and electron-poor
substrates into the corresponding imidazopyridines (4, 5 and 9).
Products (6−8) bearing halogen substituents in different ring
positions were prepared with ease and in good yields. Bromo
derivative 7 is a key intermediate to a series of ion-channel
modulaters by Gilead.17 In their patent, the preparation of 7
required isolation of the intermediate trifluoroacetamide,
followed by dehydrative cyclization with excess POCl3 (10
equiv) at 180 °C. In strong contrast, our procedure allowed for
the one-pot preparation of 7 starting from (5-bromopyridin-2-
yl)methanamine at room temperature usingonly a slight excess of
TFAA. The mildness of our reaction conditions is further
highlighted by the introduction of several sensitive functional
groups, such as heterocycles (11), esters (12), and even
unprotected alcohols (13). Many interesting trifluoromethylated
Scheme 3. Synthesis of Trifluoromethylated Imidazo-Fused N-Heterocycles from Heterocyclic Benzylamines*
*
a
Reaction conditions: heterocyclic benzylamine (1.0 equiv), NEt3 (2.5 equiv), TFAA (2.3 equiv), THF (10 vol), 0 °C to rt, 30 min. 0 °C to rt, 16 h.
b
c
d
Difluoroacetic anhydride (2.4 equiv) was used. 1 h at 0 °C. NEt3 (3.5 equiv), TFAA (3.3 equiv), 0 °C to rt, 30 min.
B
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Letter
were isolated in good to excellent yields (Scheme 4, step 2). This
means that the CF3 groups in all heterocyclic products of Scheme
4 are ultimately derived from inexpensive trifluoroacetamide
($30−100/kg)19to the best of our knowledge the first example
of using this reagent in the area of (hetero)aryl−CF3 bond
formation. The method is not without limitations, and N-
trifluoroacetamides 24j−l that are substituted in the ortho-
position to the nitrogen did not cyclize, even at elevated
temperature. In order to solve this problem, we performed
extensive screenings using 24m as model substrate (eq 1). Our
Scheme 4. Benzylation of Trifluoroacetamide with Benzyl
Halides or Tosylates and Subsequent Cyclization*
preliminary data suggest that the cyclization of this sterically
encumbered substrate is possible by activating the amide
functionality with triflic anhydride (Tf2O) and DIPEA allowing
for the formation of 25m, albeit in low isolated yield (see the SI
for further information).21
Finally, and with a scalable route for 3 in hand, we investigated
additional functionalization strategies for this building block
(Scheme 5). Bromination and iodination at the activated 8-
position proceeded with ease and delivered the halogenated
products 26 and 29 in high yields and excellent purity on 5.0 g
scale. Both products crystallized directly from the reaction
mixture after quench with a basic aqueous solution of Na2S2O3.
The halogenated derivatives were successfully transformed into
the corresponding biaryl 27 (via Suzuki coupling, b), alkyne 28
(via Sonogashira coupling, c), diarylethene 30 (via Heck reaction,
e), thioether 31 (via Pd-cat. thiolation, f), and nitrile 32 (via
cyanation with CuCN, g). Trifluoromethylated imidazo-fused
acrylate 34 was synthesized via Vilsmeier−Haack reaction,
followed by treatment of the resulting aldehyde 33 with ethyl
(triphenylphosphoranylidene)acetate. Finally, the aromatic part
of the pyrimidine ring was selectively reduced via hydrogenation
with H2 over Pd/C, and the tetrahydro derivative 35 isolated in
good yield.
*
Reaction conditions: Step 1: benzyl substrate 23a−l (1.0 equiv),
trifluoroacetamide (1.7 equiv), Cs2CO3 (2.0 equiv), THF (20 vol), 0
°C to rt, 16 h. Reaction conditions: Step 2: heterocyclic N-
trifluoroacetamide 24a−l (1.0 equiv), NEt3 (1.3 equiv), TFAA (1.2
a
b
equiv), THF (10 vol), 0 °C to rt, 30 min. 65 °C, 16 h. 0 °C to rt, 16
c
h. 60 °C. n.r. = no reaction.
benzyl tosylate 23e was used, and N-trifluoroacetamide 24e was
obtained in good yield. At elevated temperatures, benzyl
chlorides proved to be viable starting materials, and normally
80−99% conversion into the corresponding N-trifluoroaceta-
mides was achieved (after 16 h). Despite the incomplete
conversion, products 24d and 24g were isolated in excellent
purity (>99% a/a) on 5 and 2 g scale, respectively, via
crystallization of the crude material from isopropyl alcohol,
highlighting the innate potential of this reaction toward scale up.
The transformation of the benzyl N-trifluoroacetamides into the
imidazo-fused N-heterocycles proceeded smoothly using a slight
excess of base and TFAA, and the trifluoromethylated products
The enormous potential of trifluoroacetic anhydride (TFAA)
and trifluoroacetamide in the area of trifluoromethylation
chemistry is evident: the commercial availability on ton scale,
a
Scheme 5. Functionalization Strategies of 6-(Trifluoromethyl)imidazo[1,5-a]pyrimidine (3)
a
Conditions: (a) 3, NBS, MeCN, 0 °C, 30 min; (b) 26, p-MeC6H4B(OH)2, Pd(dppf)Cl2, K3PO4, 1,4-dioxane/H2O 5:1, 85 °C, 16 h; (c) 26, 3-
ethynylanisole, DIPEA, MeCN, 60 °C, 16 h; (d) 3, NIS, TFA, MeCN, 0 °C, 30 min; (e) 29, p-NC-styrene, Pd(OAc)2, P(o-tol)3, NEt3, DMF, 80 °C,
16 h; (f) 29, 3-methoxybenzenethiol, Pd2dba3, Xantphos, DIPEA, 1,4-dioxane, 110 °C, 16 h; (g) 29, CuCN, DMSO, 100 °C, 5 h; (h) 3, POCl3,
DMF, 1,2-dichloroethane, 55 °C, 16 h; (i) 33, ethyl (triphenylphosphoranylidene)acetate, CH2Cl2, 0 °C to rt, 2 h; (j) 3, Pd/C, H2 (3 bar), EtOH, rt,
2 h. See Supporting Information for reaction details and procedure.
C
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2012, 134, 9034. For a minireview on the topic, see: (f) Studer, A. Angew.
Chem., Int. Ed. 2012, 51, 8950.
low price, and high atom-efficiency make these reagents very
attractive for scale up. The use of TFAA as dehydrating and CF3-
reagent allowed us to develop a robust route for 6-
(trifluoromethyl)imidazo[1,5-a]pyrimidine (3) from commer-
cially available pyrimidin-2-ylmethanamine HCl (1). Our
optimized conditions were also applicable to other heterocyclic
benzylamines, and a wide range of novel trifluoromethylated
imidazo-fused N-heterocycles were prepared. In addition, we
have also developed a method for the synthesis of heteroaromatic
benzylic N-trifluoroacetamides via the direct alkylation of
trifluoroacetamide with benzyl halides or tosylates. The
symbiosis of the two methods compliments emerging protocols
for the synthesis of trifluoromethylated heterocycles, and we
expect that both methods will find widespread applications in
academic and industrial organic chemistry laboratories.
(5) (a) Cho, E. J.; Senecal, T. D.; Kinzel, T.; Zhang, Y.; Watson, D. A.;
Buchwald, S. L. Science 2010, 328, 1679. (b) Zanardi, A.; Novikov, M. A.;
Martin, E.; Benet-Buchholz, J.; Grushin, V. V. J. Am. Chem. Soc. 2011,
133, 20901. (c) Morimoto, H.; Tsubogo, T.; Litvinas, N. D.; Hartwig, J.
F. Angew. Chem., Int. Ed. 2011, 50, 3793. For reviews on the topic, see:
(d) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683.
(e) Tomashenko, O. A.; Grushin, V. V. Chem. Rev. 2011, 111, 4475.
(6) For reviews on the topic, see: (a) Charpentier, J.; Fruh, N.; Togni,
̈
A. Chem. Rev. 2015, 115, 650. (b) Umemoto, T. Chem. Rev. 1996, 96,
1757. (c) Barata-Vallejo, S.; Lantano, B.; Postigo, A. Chem. - Eur. J. 2014,
̃
20, 16806.
(7) For two selected examples of a large scale trifluoromethylation
using methyl chlorodifluoroacetate (MCDFA), see: (a) Mulder, J. A.;
Frutos, R. G.; Patel, N. D.; Qu, B.; Sun, X.; Tampone, T. G.; Gao, J.;
Sarvestani, M.; Eriksson, M. C.; Haddad, N.; Shen, S.; Song, J. J.;
Senanayake, C. H. Org. Process Res. Dev. 2013, 17, 940. (b) Maddess, M.
L.; Scott, J. P.; Alorati, A.; Baxter, C.; Bremeyer, N.; Brewer, S.; Campos,
K.; Cleator, E.; Dieguez-Vazquez, A.; Gibb, A.; Gibson, A.; Howard, M.;
Keen, S.; Klapars, A.; Lee, J.; Li, J.; Lynch, J.; Mullens, P.; Wallace, D.;
Wilson, R. Org. Process Res. Dev. 2014, 18, 528.
(8) For a cost comparison of trifluoromethylating reagents, see the
Supporting Information of ref 11 and: (a) Steiner, H. Chim. Oggi 2015,
33, 26. (b) McReynolds, K. A.; Lewis, R. S.; Ackerman, L. K. G.;
Dubinina, G. G.; Brennessel, W. W.; Vicic, D. A. J. Fluorine Chem. 2010,
131, 1108.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b03291.
Experimental details and spectral data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gabriel.schaefer@idorsia.com.
ORCID
(9) Fiederling, N.; Haller, J.; Schramm, H. Org. Process Res. Dev. 2013,
17, 318.
(10) (a) Swarts Reaction. Comprehensive Organic Name Reactions and
Reagents; Wiley: Hoboken, NJ, 2010. (b) Siegemund, G.; Schwertfeger,
W.; Feiring, A.; Smart, B.; Behr, F.; Vogel, H.; McKusick, B.; Kirsch, P.
Fluorine Compounds, Organic. Ullmann’s Encyclopedia of Industrial
Chemistry; Wiley-VCH: Weinheim, 2016.
Gabriel Schafer: 0000-0002-7792-9542
̈
Notes
The authors declare no competing financial interest.
(11) Beatty, J. W.; Douglas, J. J.; Cole, K. P.; Stephenson, C. R. J. Nat.
Commun. 2015, 6, 7919.
ACKNOWLEDGMENTS
(12) The use of sodium hydride (NaH) on scale poses safety hazards.
Thermal runaways of NaH-containing reaction mixtures are well
documented: (a) Buckley, J.; Lee, R.; Laird, T.; Ward, R. Chem. Eng.
News 1982, 60, 4. (b) DeWall, G. Chem. Eng. News 1982, 60, 5.
(13) Chromatographic purification on scale, should be avoided
whenever possible, as it leads to huge solvent and silica gel waste.
(14) % a/a corresponds to area purity by LC/MS. % w/w corresponds
to weight purity by 1H NMR against 1,4-dimethoxybenzene as internal
standard.
(15) Dilution of reaction mixtures are expressed in volumes (vol) and
corresponds to volumes of solvent per gram of limiting starting material
(e.g., 10 vol = 10 mL of THF/1 g of heterocyclic benzylamine).
(16) All reactions were carried out on 0.25−1.0 g scale and the products
isolated via chromatographic purification.
■
We thank Franco
̧
is Le Goff (Idorsia) for high-resolution mass
spectrometry, Kristina Kamin (Idorsia) and Christian Geugelin
(Idorsia) for IR measurements, and Dr. Thomas Weller (Idorsia)
for support of the project.
DEDICATION
■
Dedicated to our CEO Dr. Jean-Paul Clozel for the successful
launch of Idorsia Pharmaceuticals, Ltd.
REFERENCES
■
(1) (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis Reactivity
Applications, 2nd ed.; Wiley-VCH: Weinheim, 2013. (b) Organo-Fluorine
Compounds. Methods of Organic Chemistry, Houben-Weyl, E10; Thieme
Verlag: Stuttgart, 1999. (c) Groult, H.; Leroux, F.; Tressaud, A. Modern
Synthetic Processes and Reactivity of Fluorinated Compounds; Elsevier
Science: London, 2017.
(17) Corkey, B.; Elzein, E.; Jiang, R.; Kalla, R.; Kobayashi, T.; Koltun,
D.; Li, X.; Notte, G.; Parkhill, E.; Perry, T.; Zablocki, J. (Gilead Palo Alto,
Inc. USA). Fused Heterocyclic Compounds as Ion Channel Modulators.
US Patent 21521 A1, 2011.
(18) To our surprise, in most cases, the expected trifluoromethylated
imidazo-fused N-heterocyclic product was not observed by LC/MS and
the reaction proceeded via direct conversion of the intermediate N-
trifluoroacetamide into the overacylated product. The Friedel−Crafts-
type acylation of imidazo-fused N-heterocycles with TFAA is described
in: Tverdiy, O. D.; Chekanov, M. O.; Savitskiy, P. V.; Syniugin, A. R.;
Yarmoliuk, S. M.; Fokin, A. A. Synthesis 2016, 48, 4269.
(19) Price according to Manchester Organics online catalog.
(20) For a recent review on the importance of difluoromethylated
compounds, see: Yerien, D. E.; Barata-Vallejo, S.; Postigo, A. Chem. - Eur.
J. 2017, 23, 14676.
(2) (a) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
̈
́ ́
(b) Hagmann, W. K. J. Med. Chem. 2008, 51, 4359. (c) Begue, J.-P.;
Bonnet-Delpon, D. Bioorganic and Medicinal Chemistry of Fluorine;
Wiley: Hoboken, NJ, 2008.
(3) (a) Alonso, C.; de Marigorta, E. M.; Rubiales, G.; Palacios, F. Chem.
Rev. 2015, 115, 1847. (b) Liang, T.; Neumann, C. N.; Ritter, T. Angew.
Chem., Int. Ed. 2013, 52, 8214.
(4) (a) Fujiwara, Y.; Dixon, J. A.; O’Hara, F.; Funder, E. D.; Dixon, D.
́
D.; Rodriguez, R. A.; Baxter, R. D.; Herle, B.; Sach, N.; Collins, M. R.;
Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95. (b) Ji, Y.; Brueckl, T.;
Baxter, R. D.; Fujiwara, Y.; Seiple, I. B.; Su, S.; Blackmond, D. G.; Baran,
P. S. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 14411. (c) O’Brien, A. G.;
Maruyama, A.; Inokuma, Y.; Fujita, M.; Baran, P. S.; Blackmond, D. G.
Angew. Chem., Int. Ed. 2014, 53, 11868. (d) Nagib, D. A.; MacMillan, D.
W. C. Nature 2011, 480, 224. (e) Ye, Y.; Sanford, M. S. J. Am. Chem. Soc.
(21) Similar conditions have been described previously for the
cyclization of N-(2-pyridinylmethyl)benzamide and derivatives:
Pelletier, G.; Charette, A. B. Org. Lett. 2013, 15, 2290.
D
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