A convenient and efficient C-OH bond activation, PdCl2(PPh3)2catalyzed, C-C bond formation of tautomerizable quinolinones with the aid of BOP reagent and boronic acids

Article abstract of DOI:10.1039/c4ra05161k

An efficient, highly chemoselective PdCl₂(PPh₃)₂catalyzed, C-C bond formation of tautomerizable quinolinones with various boronic acids via C-OH bond activation using benzotriazol-1-yloxytris(dimethylamino) phosphonium hexafluorophosphate (BOP) reagent in the presence of K₂CO₃/1,4-dioxane system under aqueous condition, leads to the formation of functionalized quinolines in excellent yields, which offers great utility advantages in the synthesis of interesting compounds. This journal is

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A convenient and efficient C-OH bond activation, PdCl2(PPh3)2
catalyzed, C-C bond formation of tautomerizable quinolinones with the
aid of BOP reagent and boronic acids
Yadavalli Suneel Kumara, C. Dasarathana, Kamalakannan Prabakarana, Fazlur-Rahman Nawaz
b
b
b
Khana*,b* Euh Duck Jeong , Eun Hyuk Chung Hyun Gyu Kim
*
5
,
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
An efficient, highly chemoselective PdCl2(PPh3)2 catalyzed, C-C bond formation of tautomerizable quinolinones with various boronic
acids via C-OH bond activation using benzotriazol-1-yloxytris(dimethylamino) phosphonium hexafluorophosphate (BOP) reagent in the
10 presence of K2CO3 /1,4-dioxane system under aqueous conditions, leads to the formation of functionalized quinolines in excellent yields
which offers great utility, advantageous in the synthesis of interesting compounds.
challenging when compated to the Csp3–OH bond which is due to
the high energy barrier and the aromatic ring stability. However
Introduction
Natural and synthetic quinolines and their analogs (Fig. 1)
possess interesting biological properties which are also useful
15 synthetic building blocks in organic chemistry.1-9 The quinoline
structural moiety possesses wide range of biological activities
including antibacterial, antifungal, analgesic properties,10-16
Kang and his co-workers demonstrated an effective method for
50 the activation of the Csp2–OH bond of tautomerizable
heterocycles with phosphonium salts in the formation of the C–N
bond. Recently, Kang and co-workers91 reported the Pd-catalyzed
cross-coupling reactions of wide variety of tautomerizable
heterocycles with aryl boronic acids via C-OH bond activation
55 using phosphonium salts bromotripyrrolidinophosphonium
hexafluoro phosphate (PyBroP) as activating reagents. This
involved heterocycle-Pd(II)−phosphonium intermediate species
in the mechanism.
antituberculosis,17-23
antimalarial,24-27
anti-inflammatory,28
anticancer, 29 antibiotic,30 antihypertensive,31 and anti-HIV
20 activities.32-34 The quinolines containing alkyl, alkenyl chains at
the 2-potision have shown promising activity against several
Leishmania
strains.35-37
Halogen-containing
quinolines
demonstrates potential bioactivity and the chloro functionalality
plays a great source in further structural mdofications.38-44 In spite
25 of wide range of pharmacological activities and numerous reports
45-54
The authors also achieved the synthesis of 6-arylpurine
60 ribonucleoside without any protection-activation-coupling-
deprotection sequence. This procedure demonstrated an excellent
reactivity and chemoselectivity even with hindered boronic acids.
This methodology have rendered numerous opportunities and
also provided an attractive route for the direct arylation of
65 tautomerizable heterocyclics via functionalization of activated C–
OH bond. And can be used as a nucleophile substitution for
potential heterocyclics (Fig 2). Abhishek et al., achieved direct
cross-coupling of tautomerizable heterocycles through PyBroP-
mediated, microwave assisted and Pd/Cu-catalyzed sequential C–
70 OH/C–H activation for symmetrical 1,2-, 1,3-, and 1,4-bidiazine
units (Fig 2).92, 93 Similarly direct alkynylation of tautomerizable
heterocylcles has been achieved by Kang et al via the alkyne C-
H/tautomerizable heterocycles C−OH activation by PyBrOP
followed by dehydrative cross coupling -Sonogashira coupling
75 with alkyl or aryl terminal alkynes, alkenyl and also with
alkynylalcohols. The alkynes bearing a hydroxyl group also
reacted smoothly without any protection–deprotection step. The
reactions invoved Pd/Cu-catalyst for effective Csp2- Csp bond
formations (Fig 2).94-96. Aldrich et al utilized PdCl2(CH3CN)2,
80 (P(Cy)2Biphenyl 2-yl, Cs2CO3 system and in the absence of CuI
using the modified strategy. They have also achieved 6-
alkynylpurine ribonucleoside derivatives showing potential
of their synthetic methods,
there is a need for the
development of a new, simple, convenient, and environmentally
benign synthetic approaches for the 2-substituted quinolines
using mild conditions remains an active research area.
30
Quinolines substituted at the 2-position shows in vivo activities
against Leishmania donovani55-57 and are in its preclinical
development.58-61 In addition, some compounds display
62-
substantial antiviral activity in HIV-infected cells,
67anticancer,68-72 antimalarial activities.73-78
35 A number of methods have been developed for the synthesis of 2-
substituted quinolines.9-88 However, so far there is no direct
report available for the synthesis of 2-substituted quinolines from
its amide analog and boronic acids. The reported methods involve
Suzuki coupling of 2-halo substituted quinolines with various
40 boronic acids.89,90 Multistep reaction sequences, harsh conditions
and sometimes toxic reagents such as POCl3 were involved for
the preparation of chloro intermediate which gave lower or
moderate yields. In order to overcome these difficulties and to
ease the synthesis of 2-substituted quinolines, researchers took an
45 effort to expedite a direct arylation.
It must be noted that aromatic Csp2–OH activation is highly
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2).97
cytostatic activity
5
The PyBroP-mediated coupling of 3,4-Dihydropyrimidin-
2(1H)-one with various
nucleophiles to
give the
multifunctionalized pyrimidines have also been reported (Fig
F
HN
F
F
OH
HO
N
Cl
OH
N
O
F
OH
O
OH
O
N
F
S
F
F
F
N
O
F
NH
Xanthurenic acid
OH
Mefloquine
N
O
NH2
Montelukast
Tafenoquine
F
N
HO
OH OH
O
O
OH
N
Br
R2
NH
N
N
O
N
O
N
R1
NH
N
Pitavastatin
Bedaquiline
R3
O
O
H
N
O
O
O
O
NH2
OH
Cl
N
H
R4
N
N
N
O
O
N
N
R5
R6
N
N
Cl
O
R8
R7
Imazaquin
O
Pipequaline
R5 =R6 OCH3, H
Abanoquil
R7=R6 CH3, H, OCH3
H
N
OH
OH
O
O
O
S
Cl
Cl
Cl
COOEt
O
N
S
N
R9
N
N
Cl
R9 = -CH3 -CH2Pip
Oxycinchophen
Cl
Fig 1 Biologically important 2- or 2,4-substituted quinolines
2
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N
O
B(OH)2
N
HO
O
+
N
O
N
NH
HO
OH
N
HO
N
O
N
HO
OH
O
OMe
HN
+
NuH
O
N
OMe
N
H
Nu
N
HN
NH
F
F
HN
N
or
O
N
P-
F
F
F
X
F
or
P+
X
N
Br
HN
X
N
N
PyBroP
OH
R
N
R
N
N
+
N
R = CH2OH, Ph, Tolyl, Anisyl, thiophenyl, cyclohexenyl, (CH2)4OH
R
R
OH
N
+
N
R
N
OMe
OMe
N
Cl
OMe
R
N
N
Cl
O
R
N
N
NH
N
N
N
N
+
R
N
O
O
O
R =Ph, TES
O
O
OAc
O
OAc
Fig 2 Tautomerizable heterocycles in PyBroP mediated reactions91-97
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O
Nu
X
NH
X
N
X = CR, NH
F
F
F
F
F
NuH = NHR1R2,
N- heterocycles,
P
F
N
N
P
O
N
Ar-OH, Ar-SH
N
N
N
O
BOP
Nu
HN
X
N
X
X = Ch or C-R, N
Nu' = Alkyl and amines
( thio)phenols,imidazoles
H
NH
NH
N
N
N
N
O
N
HO
N
N
N
N
H
Kinetin
Olomoucine
Fig 3 Tautomerizable heterocycles in BOP mediated reactions98,99
10 With our longstanding interest in the synthesis and diversification
of heterocycles, particularly in quinoline chemistry,100-113 we
became very interested in applying the C-OH activation strategy
with other types of cross-coupling reactions. Herein, we report
our studies of the Suzuki-type reactions of tautomerizable
15 heterocycles activated by BOP reagent with various boronic acids
(Scheme 1).
Further, the aromatic nucleophilic substitution of cyclic amides
with nitrogen nucleophiles, phenols, thiophenol nucleophiles
were achieved using benzotriazol-1-yloxytris(dimethylamino)
phosphonium hexafluorophosphate (BOP) (Fig 3).98, 99 Similarly
the microwave-assisted palladium-catalyzed phosphonium
coupling of tautomerizable heterocycles for efficient C−C cross-
coupling has been reported.
5
i)
BOP (1.5 eq.),Et3N (3.0 eq.)
1,4-Dioxane (10 mL)
Heated at 100 °C, 2 h
(2.0 eq.)
H
N
N
R4
R1
O
ii)
R4 B(OH)2
PdCl2(PPh3)2 (2.5 mol %)
R3
R3
R1
R2
R2
K2CO3 (3.0 eq.), water (1 mL)
Heated at 100 °C, 12 h
1, 2, 3
4, 5, 6
R1= COOEt, R2= 2-Cl-Phenyl, R3= Cl, 1
R1= COCH3, R2= 2-Cl-Phenyl, R3= Cl, 2
R1= COOEt, R2= 2-Cl-Phenyl, R3= Cl, 4
R1= COCH3, R2= 2-Cl-Phenyl, R3= Cl, 5
R1= CHO, R2= H, R3= H, 6
23 examples
R1= CHO, R2= H, R3= H, 3
Scheme 1. General scheme for the synthesis of 2-substituted quinolines
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Table 1. Coupling of 3-substituted quinolin-2(1H)one with phenyl boronic acid: Optimization of the reaction conditions using
PyBroP reagenta
i)
PyBroP, Et3N
H
1,4-Dioxane (10 mL)
Heated at 100 °C, 2 h
N
Ph
N
O
ii)Ph B(OH)2
CHO
Catalyst (2.5 mol %)
Base, water (1 mL)
Heated at 100 °C, 12 h
CHO
3a
6a
Entry
1
Catalyst/ mol %
PdCl2(PPh3)2/10
PdCl2(PPh3)2/5
PdCl2(PPh3)2/10
Pd(OAc)2/10
Solvent
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Yield (%)b
49
2
36
39c
3
4
15
5
Pd(OAc)2/5
Traces
21
6
Pd2(dba)3/10
7
Pd2(dba)3/5
Traces
26
8
PdCl2(dppf):DCM /10
PdCl2(dppf):DCM /5
9
Traces
10
11
12
13
14
15
PdCl2(PPh3)2/10
PdCl2(PPh3)2/10
Dioxane
DMF
47d
35
PdCl2(PPh3)2/10
PdCl2(PPh3)2/10
PdCl2(PPh3)2/10
DCM
THF
Traces
Tracess
32
Toluene
PdCl2(PPh3)2/10
CH3CN
43
aReaction Conditions: i) Amide (1 mmol, 1.0 equiv.), PyBroP (1.5 equiv.), Et3N (3.0 equiv.) in 1,4-dioxane (10 ml) at 100 °C for 2h, ii)
PdCl2(PPh3)2 (10 mol%), K2CO3 (3.0 equiv.), boronic acid (2 equiv.), and water (1 mL) at 100°C for 12h; bisolated yield.. cK3PO4 (3.0 equiv.),,
dNa2CO3 (3.0 equiv.).
Table 2. Coupling of 3-substituted quinolin-2(1H)one with phenyl boronic acid: Optimization of the reaction condition using BOP
reagenta
i)
BOP, Et3N
H
1,4-Dioxane (10 mL)
Heated at 100 °C, 2 h
N
Ph
N
O
ii)
Ph B(OH)2
CHO
Catalyst (2.5 mol %)
Base, water (1 mL)
Heated at 100 °C, 12 h
CHO
3a
6a
Yield (%)b
85
Entry
Catalyst/ mol %
PdCl2(PPh3)2/10
PdCl2(PPh3)2/5
PdCl2(PPh3)2/10
Pd(OAc)2/10
Pd(OAc)2/5
1
2
3
4
5
6
77
52c
Traces
Traces
32
Pd2(dba)3/10
7
8
9
10
11
Pd2(dba)3/5
Traces
39
PdCl2(dppf):DCM /10
PdCl2(dppf):DCM /5
PdCl2(PPh3)2/10
Traces
56d
PdCl2(PPh3)2/10
15-60e
aReaction Conditions: Amide (1 mmol, 1.0 equiv.), BOP (1.5 equiv.), Et3N (3.0 equiv.) in 1,4-dioxane (10 ml) at 100 °C for 2h and then
PdCl2(PPh3)2 (10 mol%), K2CO3 (3.0 equiv.), boronic acid (2 equiv.), and water (1 mL) at 100 °C for 12h; bisolated yield. cK3PO4 (3.0 equiv.),,
dNa2CO3 (3.0 equiv.), eDMF 50%, DCM 15%, THF 22%, Toluene 53%, CH3CN 60%
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Table 3 Synthesis of 2-aryl -3-carbethoxy-6-chloroquinolines and2-aryl -3-acetyl-6-chloroquinolinesa a
BOP (1.5 eq.),Et N (3.0 eq.)
i)
3
H
N
N
R4
R1
1,4-Dioxane (10 mL)
Heated at 100 °C, 2 h
O
(2.0 eq.)
R4 B(OH)2
ii)
R3
R3
R1
PdCl2(PPh3)2 (2.5 mol %)
R2
R2
K2CO3 (3.0 eq.), water (1 mL)
4a-e
1
Heated at 100 °C, 12 h
R1= COOEt, R2= 2-Cl-Phenyl, R3= Cl, 1
R1= COOEt, R2= 2-Cl-Phenyl, R3= Cl, 4a-e
O
O
N
O
N
N
N
O
Cl
O
Cl
Cl
Cl
O
Cl
O
Cl
O
4c(89%)
4b(84%)
4a(82%)
O
S
N
N
O
O
Cl
Cl
Cl
O
Cl
O
4e(81%)
4d(90%)
i)
BOP (1.5 eq.),Et3N (3.0 eq.)
1,4-Dioxane (10 mL)
H
N
N
R4
R1
O
Heated at 100 °C, 2 h
(2.0 eq.)
ii)
R4 B(OH)2
R3
R3
R1
PdCl2(PPh3)2 (2.5 mol %)
4
R2
5a-f
R2
K2CO3 (3.0 eq.), water (1 mL)
Heated at 100 °C, 12 h
R1= COCH3, R2= 2-Cl-Phenyl, R3= Cl
R1= COCH3, R2= 2-Cl-Phenyl, R3= Cl
F
O
N
N
N
OMe
Cl
Cl
Cl
O
Cl
Cl
O
Cl
O
5b (70%)
5c (78%)
5a (89%)
CO2Et
N
S
O
O
N
N
N
Cl
Cl
Cl
Cl
O
Cl
Cl
O
5f (80%)
5e (73%)
5d (79%)
aReaction Conditions: Amide (1 mmol, 1.0 equiv.), BOP (1.5 equiv.), Et3N (3.0 equiv.) in 1,4-dioxane (10 ml) at 100 °C for 2h and then PdCl2(PPh3)2 (10
mol%), K2CO3 (3.0 equiv.), boronic acid (2 equiv.), and water (1 mL) at 100 °C for 12h; isolated yield.
6
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Table 4 Synthesis of 2-aryl -3-formyl-6-chloroquinolines a
i)
BOP (1.5 eq.),Et3N (3.0 eq.)
1,4-Dioxane (10 mL)
H
N
N
R4
R1
O
Heated at 100 °C, 2 h
(2.0 eq.)
ii)
R4 B(OH)2
PdCl2(PPh3)2 (2.5 mol %)
R3
R3
R1
3
R2
6a-l
R2
K2CO3 (3.0 eq.), water (1 mL)
Heated at 100 °C, 12 h
R1= CHO, R2= H, R3= H
R1= CHO, R2= H, R3= H
Cl
N
N
N
N
H
H
H
O
O
6c(89%)
N
O
O
6b(81%)
6a(88%)
MeO
N
N
H
Cl
N
H
H
O
O
6e(77%)
6f(71%)
6d(73%)
OMe
CHO
N
N
CF3
H
H
N
O
6i(81%)
O
CN
6h(71%)
6g(83%)
CHO
S
CHO
N
CHO
F
N
N
6 l(79%)
6j(72%)
6k(82%)
Cl
aReaction Conditions: Amide(1 mmol, 1.0 equiv.), BOP(1.5 equiv.), Et3N(3.0 equiv.) in 1,4-dioxane (10 ml) at 1000C for
2h and then PdCl2(PPh3)2 (10 mol%), K2CO3 (3.0 equiv.), boronic acid( 2 equiv.), and water( 1 mL) at 1000C for 12h;
isolated yield.
N
H
N
O
N
O
P
N
N
PF6
Et3N, BOP
1,4-Dioxane,
Heating
R3
R1
R3
R1
I
R2
R2
N
R4
R1
Pd0
L2
R3
R2
L
N
Pd
L
R4
IV
L
N
N
O
PF6
N
Pd
L
P
N
R3
R1
R2
R3
R1
II
R2
K2CO3 + H2O
B(OH)4
K
L
III
OH
N
Pd
L
K2CO3
H2O
N
P
N
R3
R1
R4-B(OH)3
K
R4-B(OH)2
PF6
K
O
N
R2
Scheme 2 Possible mechanism of the reaction
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Encouraged by the results obtained through optimized direct
60 arylation, we embarked on an investigation of the reaction scope.
Several of tautomerizable 3-formyl, 3-acetyl, 3-carbethoxy
quinolin-2-ones containing substitutions at varied positions were
examined for the Pd-catalyzed direct arylation via C-OH bond
activation using BOP reagent (Scheme 1, Table 3,4). The tested
65 tautomerizable quinolines with electronegative nitrogen atom,
electron-withdrawing acetyl, carbetoxy groups facilitate the
phosphonium coupling reactions. The Pd-catalyzed BOP
mediated phosphonium coupling condition was quite efficient for
the direct arylation of these tested tautomerizable quinolines with
70 various electron-rich and electron-poor aryl boronic acids through
the heterocycle-phosphonium salt to afford the biaryl products.
The reaction conversion was good and produced excellent
isolated yields. Heteroaryl and sterically hindered aryl boronic
acids also efficiently furnished the biaryl products in high yields.
75 The list of synthesized compounds using this novel method is
summarized in Table 3, 4. We have recognized the
chemoselectivity of the reaction as amplified in the direct
arylation of quinolinones containing chloro, enolisable acetyl as
well as carbethoxy which remained intact during the reaction.
80 Hence phosphonium coupling shows remarkable functionality
compatibility. Therefore, have great utility, advantageous useful
in the synthesis of many biologically interesting compounds.
Results and Discussion
Kang et al. established PyBroP (bromotripyrrolidinophosphonium
hexafluorophosphate) as the most suitable activator for in situ
activation of phenolic C–O bonds,. With the above preliminary
idea in mind, we continued the research on with diverse
tautomerizable heterocycles and boronic acids. Initially explored
a wide range of conditions for direct alkylation of the substrate 3-
formyl quinolin-2(1H)one with phenyl boronic acid. The 3-
formyl quinolin-2(1H)one was first activated in situ using
5
10 PyBroP (1.5 eq.) and triethylamine (3 eq.) in 1,4-dioxane at
100 °C for 2 h. And then cross-coupling conditions have been
developed for Suzuki coupling reactions (Table 1).
For the initial study, we followed Kang et al., condition using
15 PyBroP for in situ actiavtion. Surprisingly, the tested 3-
substituted quinolin-2(1H)one coupled with phenyl boronic acid
(Table 1), but offered a poor yield. In order to get a good
conversion, we screened the reaction with various palladium
catalysts including Pd(OAc)2, Pd2(dba)3 and PdCl2(dppf):DCM
20 using a PyBroP activator, however lower yields less than 50%
were obtained (Table 1, entry 1-10). While using 10 mol%
Pd(OAc)2, Pd2(dba)3 and PdCl2(dppf):DCM catalysts, the yield is
very low and with 5 mol% load the conversion becomes more
trace (entry 5-9). Next, we have tested with two bases such as
25 K3PO4, Na2CO3 using 10 mol% of PdCl2(PPh3)2 catalyst, but the
results showed lower yield (Table 1, entry 3, 10). It must be noted
that mild carbonate bases and water presence is essential for a
neat conversion. In the absence of water, the reaction gave
sluggish products. Further the effect of the solvent on this
30 phosphonium coupling was investigated. Among the tested
organic solvents e.g., 1,4-dioxane, DCM, DMF, THF, CH3CN,
the polar solvents 1,4-dioxane, CH3CN was successful due to the
solubility of intermediate heterocycle-phosphonium salts and the
solvents toluene and DMF were the least efficient
We propose the following mechanism for the direct arylation of
85 tautomerizable heterocycles, based on the Kang et al., (Scheme 2)
study. The tautomerizable heterocycle is first activated by BOP in
the presence of triethylamine to afford the phosphonium salt I.
Once the active Pd(0) species is formed, the catalytic cycle
begins with the oxidative addition of the phosphonium salt I to
90 generate Pd(II) complex II. Next the reaction with a K2CO3 base
producing the heterocycle-Pd(II)-OH species III. Followed by
transmetalation of the heterocycle-Pd(II)-OH species with the
activated aryl boron-ate complex giving the heterocycle-Pd(II)
aryl species IV. This undergoes reductive elimination to afford
95 the cross-coupling product and regenerate the Pd(0) species.
The overlap of the NMR spectra of a starting material and the
phosphonium salt intermediate formed in the first stages is
provided as an evidence for its formation along with the 31P NMR
of the phosphonium salt as seen in the supporting document
35
In order to further increase the product yield, varied the activator
to BOP (OBt-derived) reagent was used instead of PyBroP (Br-
derived reagents) for a more effective reaction as summarized in
Table 2. The results encouraged us to use 3-formyl quinolin-
40 2(1H)one which underwent smooth coupling with phenyl boronic
acid in the presence of the 10 mol% of PdCl2(PPh3)2 catalyst,
K2CO3 as the base and 1,4-dioxane solvent under aqueous
conditions. With this good result, we have tested the coupling
reaction using BOP activator with various catalytic conditions
45 and solvents. The results are summarized in Table 2. We are
pleased to inform that the coupling reaction of 3-formyl quinolin-
2(1H)one with phenyl boronic acid was successfully achieved in
a one-pot manner through in situ activation using BOP reagent
(1.5 eq.), Et3N base(3.0 eq.) and 1,4-dioxane solvent under reflux
50 conditions . After which the subsequent coupling reaction to the
same mixture with the addition of 10 mol% of PdCl2(PPh3)2
catalyst, K2CO3 base (3.0 eq.) and water (1 mL under reflux
conditions was observed.
100 Conclusions
In summary, we have developed an efficient and straightforward
pathway for the diverse synthesis of 2-arylated quinoline
derivatives via the one-pot cross-coupling of insitu activated 2-
OH quinoline derivatives and boronic acids. More importantly,
105 we have established a catalyst-controlled highly chemo- and
regioselective protocol for the construction of two different aryl–
aryl bonds via the one-pot procedure. The results obtained would
be of great importance because the concepts can be used to
improve the synthetic efficiency in modern organic chemistry. A
110 one pot reaction with high selectivity has been recognized as the
especially effective way for atom-efficient and environmentally
benign synthesis. Consequently, these methods should find more
practical applications in pharmaceuticals, functional materials,
catalysts, and coordination chemistry owing to the unique
115 property of 2-arylated quinolines in these areas.
Further the effect of the solvents on this phosphonium coupling
55 was investigated using a BOP as the coupling reagent. Among the
tested organic solvents 1,4-dioxane, CH3CN was succesful due to
the solubility of the heterocycle-phosphonium salts.
8
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22. A. Nayyar, A. Malde, E. Coutinho, R. Jain, Bioorg. Med. Chem.,
Acknowledgements
2006,14, 7302
The authors wish to express their gratitude to the VIT University Vellore
for support and facilities and SIF-VIT for their support of NMR (DST-
FIST Fund), GCMS and IR facilities. This work was supported by the
5 grant No. R0001026 from the Ministry of Trade, Industry & Energy and
Busan Metropolitan City, Korea.
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