Palladium-catalyzed chemoselective synthesis of indane-1,3-dione derivatives via tert-butyl isocyanide insertion

Article abstract of DOI:10.1039/c5ob00472a

A simple and efficient strategy for the synthesis of indane-1,3-dione derivatives through a palladium(0)-catalyzed reaction incorporating tert-butyl isocyanide has been developed. In addition, by applying this protocol as the key step, indenopyrazole derivatives can be easily synthesized in high yields in a one-pot procedure. This methodology is tolerant of a wide range of substrates and applicable to library synthesis.

Full text of DOI:10.1039/c5ob00472a

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DOI: 10.1039/C5OB00472A
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Palladium-catalyzed chemoselective synthesis of
indane-1, 3-dione derivatives via tert-butyl isocyanide
insertion
Cite this: DOI: 10.1039/x0xx00000x
Huaqing Duan,aZhong Chena, Li Hanb, Yulin Fengc , Yongming Zhu*aand Shilin Yang*a
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
A simple and efficient strategy for the synthesis of indaneꢀ1, 3ꢀdione derivatives through a palladium
(0)ꢀcatalyzed reaction incorporating with tertꢀbutyl isocyanide has been developed. In addition, by
applying this protocol as the key step, indenopyrazole derivatives can be easily synthesized in high
yields in a oneꢀpot procedure. The methodology is tolerant of a wide range of substrates and applicable
to library synthesis.
www.rsc.org/
with Fu group’s report.11 We varied the reaction condition in order
to insert tertꢀbutyl isocyanide into the substrate. To our delight, tertꢀ
Introduction
butyl isocyanide was successfully coupled with carbon atom of the
active methylene between the two carbonyls. So new CꢀC bond was
formed, not CꢀO bond and (1ꢀ(tertꢀbutylimino)ꢀ3ꢀhydroxyꢀ1Hꢀindenꢀ
2ꢀyl)(phenyl)methanone (Scheme 1, C) was synthesized.
During the past few decades, isocyanides insertion has emerged as
an effective strategy in modern synthetic organic chemistry, since
the pioneering work of Passerini1 and Ugi2 and subsequently related
isocyanideꢀbased twoꢀcomponent reactions3 with isocyanides
insertion into palladiumꢀcarbon bond and evolutionary
multicomponent reactions (MCRs).4 Recently, a wide range of
O
O
O
organic
compounds
including
isocoumarins,
phthalides,5
Et
Et
HN
O
CN
quinazolinones,6 6Hꢀisoindolo[2,1ꢀa]indolꢀ6ꢀones, indenoindolones,7
alkynones,8 diarylketones,9 arylaldehydes10 have been synthesized
via the insertion of isocyanides to form CꢀN , CꢀO or CꢀC bonds by
our group. However, the work about chemoselective insertion of
isocyanides to form CꢀC bond has been rarely reported, especially
when insertion of isocyanides to form CꢀO bond was also a choice at
the same time.
CN
O
O
O
P3 (Cytotoxicity)
(Pimꢀ1 kinase inhibitor)
O
(Antiallergic activity)
P1
P2
O
OCH3
N
NH
H2N
HN
NH
O
O
O
O
O
NH
NH
N
N
P4
(CDK inhibitor)
(EGFR inhibitor)
P5
Figure1. Bioactive indaneꢀ1, 3ꢀdione derivatives
Indaneꢀ1, 3ꢀdiones are important building blocks in organic
synthesis, especially for the preparation of many natural products
and pharmaceuticals.12 Indaneꢀ1, 3ꢀdione derivatives have many
biological activities, including Pimꢀ1 kinase inhibitor (P1),13
antiallergic activity (P2),14 cytotoxicity (P3),15 CDK inhibitor (P4),16
and EGFR inhibitor (P5)17. Due to the importance of indaneꢀ1, 3ꢀ
dione derivatives (Fig.1), some synthetic methodologies have been
reported. 1) Decomposition of 2ꢀdiazoꢀl,3ꢀindandione by rhodium(II)
acetate in substituted benzene resulted in overall carbonꢀhydrogen
insertion to give 2ꢀsubstituted indaneꢀ1, 3ꢀdiones.18 2) The reaction
of αꢀdiazo ketones and aldehydes in the presence of tin(II) chloride
gave indaneꢀ1, 3ꢀdiones.19 3) Furthermore, another alternative
approach was via oxidation and cyclization of 2ꢀ(2ꢀ
arylethynylphenyl) acetonitrile with palladium(II) chloride.20 It is
necessary to explore mild and high regioselective methods for the
Scheme1. An unexpected synthetic pathway
Condition 1：Pd(OAc)2, DPEPhos, K2CO3, DMF, 120 °C; Condition 2：
PdCl2(PPh3)2, LiOtBu, dioxane, 120 °C
In 2012, our group reported palladiumꢀcatalyzed synthesis of
isocoumarins and phthalides via tertꢀbutyl isocyanide insertion by
forming CꢀO bond.5 In a continuation to our interest, we tried to
synthesis (Z)ꢀ3ꢀ(2ꢀoxoꢀ2ꢀphenylethylidene)isobenzofuranꢀ1(3H)ꢀone
(Scheme 1, A2) with 1ꢀ(2ꢀbromophenyl)ꢀ3ꢀphenylpropaneꢀ1,3ꢀdione
as the substrate by applying the same reaction condition from the
above literature. 5 It was surprised that tertꢀbutyl isocyanide was not
inserted, and the major product (yield = 86%) was 2ꢀphenylꢀ4Hꢀ
chromenꢀ4ꢀone (Scheme 1, B). We suspected that there was a
competing reaction under the special condition. It was coincident
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DOI: 10.1039/C5OB00472A
11
12
13
14
15
16
17
18
PdCl2(PPh3)2
Pd(OAc)2/ PPh3
Pd(dba)2/ PPh3
PdCl2/ PCy3
K3PO4
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
trace
63%
66%
62%
58%
52%
63%d
84%e
preparation of indaneꢀ1, 3ꢀdione derivatives from commercially
available simple starting materials. Herein we report
chemoselective synthesis pathway for these valuable derivatives.
a
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
Results and discussion
According to our previous work,5 the reaction of S1-a (1.0 equiv)
with tertꢀbutyl isocyanide (1.2 equiv) was examined in DMF at 120
°C in the presence of Pd(OAc)2 (5 mol %) and DPEPhos (10 mol %)
with K2CO3 (2.0 equiv) as base. tertꢀButyl isocyanide was not
inserted and 2ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone(Scheme 1, B) was the
major product in 86% yield (Table 1, entry 1). We suspected that the
reaction selectivity may be affected by base, so we varied base from
K2CO3 to KOtBu (Table 1, entry 2). The solvent choice was critical
for the reaction (Table 1, entries 3ꢀ7). It was interesting that the
major product was also 2ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone when DMF or
CH3CN was used as solvent. However, (1ꢀ(tertꢀbutylimino)ꢀ3ꢀ
hydroxyꢀ1Hꢀindenꢀ2ꢀyl) (phenyl)methanone (3a) was synthesized in
62% yield with dioxane as solvent. When the base was switched to
LiOtBu, the yield of 3a was improved to 72% (Table 1, entries 8ꢀ
11). Pd(OAc)2 or Pd(dba)2 was selected as the Pd resource (Table 1,
entries 12ꢀ13), and the yield of 3a decreased. Then, several
phosphorus ligands were tested in this reaction (Table 1, entries 14ꢀ
16), the yield of 3a did not be improved. When the reaction
temperature varied from 120 °C to 100 °C, the yield of 3a decreased
from 72% to 63% (Table 1, entry17). To our delight, 84% yield of
3a was obtained when 3 equiv LiOtBu was used (Table 1, entry18).
Thus, the optimal reaction was performed with S1-a (1.0 mmol) in
2.0 mL of dioxane at 60 °C for 0.5 h, then tertꢀbutyl isocyanide (1.2
mmol), PdCl2(PPh3)2 (0.05mmol) and LiOtBu (3.0 mmol) were
added, the reaction was kept at 120 °C for another 2 h.
PdCl2/DPPF
PdCl2/DPEPhos
PdCl2(PPh3)2
PdCl2(PPh3)2
a Reaction conditions: All reactions were performed with S1-a (1.0 mmol),
tertꢀbutyl isocyanide (1.2 mmol), catalyst system (0.05mmol) and base (2.0
mmol) in 2.0 mL of solvent at 120 °C for 2 h. DPPF = 1,1′ꢀbis (diphenyl
phosphino)ferrocene, DPEPhos = bis [(2ꢀdiphenylphosphino) phenyl]ether.
PCy3 = tricyclohexylphosphine, PPh3 = triphenylphosphine, Pd(dba)2 = bis
(dibenzylideneacetone) palladium. b Isolated yield. c The major product was
2ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone. d Reaction at 100 °C for 2 h. e The reaction was
performed with S1-a (1.0 mmol) in 2.0 mL of solvent at 60 °C for 0.5 h.
Then tertꢀbutyl isocyanide (1.2 mmol), PdCl2(PPh3)2 (0.05mmol) and LiOtBu
(3.0 mmol) were added, the reaction was kept at 120 °C for another 2 h.
With the optimized reaction conditions in hand, we then tested the
scope and generality of this method. Various substitutes in R2,
including aryl (Table 2, entries 1ꢀ9), heteroaryl (Table 2, entries 10ꢀ
11) and alkyl (Table 2, entries 12ꢀ13), were well tolerated.
Substrates with electron rich and electron deficient functional groups
both gave good yields (Table 2, entries 1ꢀ8). Good yields were also
obtained when R2was a naphthalene or heteroaryl group (Table 2,
entries 9ꢀ11). In addition, when R2 was an aliphatic group or OEt
(Table 2, entries 12ꢀ14), the moderate yields were also obtained.
While R1 was OCH3 or F (Table 2, entries 15ꢀ16), it resulted in a
decreased yields of 56% or 54%. It seemed that R1 was closely
correlative with the reaction yield. From the NMR spectra of
O
O
OH
Pd/ligand,
base, solvent,120 oC
O
N
C
Br
N
S1-a
3a
Table1. Condition optimizations a
compounds 3a-3p, we found that there was
isomerization phenomenon.
a
ketoneꢀenol
Entry
Catalyst/ligand
Pd(OAc)2/ DPEPhos
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Base
Solvent
DMF
Yield b(%)
0c
1
K2CO3
2
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
LiOtBu
NaOtBu
LiHMDS
DMF
0c
3
CH3CN
THF
0c
4
41%
62%
trace
43%
72%
60%
36%
5
dioxane
toluene
anisole
dioxane
dioxane
dioxane
Table2. Synthesis of indaneꢀ1, 3ꢀdione derivativesa
6
Entry
1
Substrate
Product
Yield(%)b
84
7
8
S1-a
3a
9
10
2 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5OB00472A
2
3
4
S1-b
S1-c
S1-d
3b
3c
3d
65
68
71
14
15
S1-n
S1-o
3n
3o
62
56
16
S1-p
3p
54
aAll reactions were performed under N2 on a 1.0 mmol scale, using LiOtBu
(3.0 mmol) in dioxane (2.0 mL) at 60 °C for 0.5 h. Then PdCl2(PPh3)2
(0.05mmol) and tertꢀbutyl isocyanide (1.2 mmol) were added, the reactions
were kept at 120 °C for another 2 h. b Isolated yield.
5
6
S1-e
S1-f
3e
3f
63
61
To further evaluate this practical approach, a variety of substrates
with active methylene group were investigated, and the results were
summarized in Table 3.When R3 was phenyl, the insertion reaction
of 1ꢀ(2ꢀbromophenyl)ꢀ2ꢀphenylethanone with tertꢀbutyl isocyanide
successfully delivered the desired products. And 2ꢀphenylꢀ1Hꢀ
indeneꢀ1,3(2H)ꢀdione was synthesized via hydrochloric acid
hydrolysis in the yield of 66% (Table 3, entry 1). Electronꢀdonating
as well as electronꢀwithdrawing substitutes of benzene ring were
well tolerated, and yields of the former were higher than those of the
latter (Table 3, entries 2ꢀ5). In addition, as for aliphatic substitutes,
the desired products were obtained in good yields (Table 3, entries 6ꢀ
7). To our delight, the substrate with sensitive functional group such
as CN was also converted smoothly in the moderate yield (Table 3,
entry8). It was interesting that when (2ꢀbromophenyl) (cyclohexyl)
methanone was employed as the substrate, tertꢀbutyl isocyanide was
coupled with oxygen atom of enolic form by carbonyl tautomerism
7
8
S1-g
S1-h
3g
3h
72
69
and
Nꢀ(3ꢀcyclohexylideneisobenzofuranꢀ1(3H)ꢀylidene)ꢀ2ꢀmethyl
propanꢀ2ꢀamine (Scheme 2, 4i) was generated in 74% yield, which
might due to the steric hindrance. Similarly, 1ꢀ(2ꢀbromophenyl)
propanꢀ2ꢀone afforded 3ꢀmethylꢀ1Hꢀisochromenꢀ1ꢀone (Scheme 2,
5a) with further hydrochloric acid hydrolysis. It suggested that in the
optimized conditions, reaction selectivity was determined by the
structure of substrate.
9
S1-i
S1-j
3i
3j
86
76
10
1) LiOtBu, dioxane, 60 oC,
tꢀBuꢀNC, PdCl2(PPh3)2 ,120 oC
O
O
R3
R3
2) 3 M HCl, THF, rt, 2h
Br
O
11
12
13
S1-k
S1-l
3k
3l
72
53
68
S2-a - S2-h
Table3. Synthesis of indaneꢀ1, 3ꢀdiones a
4a-4h
Entry
1
Substrate
Product
Yield(%)b
S2-a
4a 66
S1-m
3m
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DOI: 10.1039/C5OB00472A
O
On the basis of the above experimental results and the related
literature,5 a plausible mechanism for this reaction is outlined in
Scheme 4. With the assistance of LiOtBu, the intermediate 6 is
generated from S2-a. Oxidative addition of 6 to the Pd(0) catalyst
leads to a Pd(Ⅱ) complex 7, followed by tertꢀbutyl isocyanide
2
S2-b
S2-c
4b 75
Br
insertion to form 8. Reductive elimination of
8 gives the
3
4c 73
intermediate 9，which yields product 4a by acid hydrolysis.
4
5
6
7
S2-d
S2-e
S2-f
S2-g
4d 62
4e 61
4f
76
4g 63
Scheme4. Plausible mechanism for the synthesis of 4a
Conclusions
8
S2-h
4h 61c
In summary, we have developed a simple and efficient strategy for
chemoselective synthesis of indaneꢀ1,3ꢀdione derivatives from easily
accessible substrates and tertꢀbutyl isocyanide. This approach, which
provides one of the easiest pathways for this class of valuable
compounds, uses PdCl2(PPh3)2 as the catalyst system and LiOtBu as
base. Furthermore, indenopyrazole derivatives can be easily
synthesized in high yields in a oneꢀpot procedure by applying this
protocol as the key step. Characterized by mild reaction conditions
and moderate to excellent yields, this method may be very attractive
in synthetic organic and medicinal chemistry.
a All reactions were performed under N2 on a 1.0 mmol scale, using LiOtBu
(3.0 mmol) in dioxane (2.0 mL) at 60 °C for 0.5 h. Then PdCl2(PPh3)2
(0.05mmol) and tertꢀbutyl isocyanide (1.2 mmol) were added, the reactions
were at 120 °C for another 2 h, followed by hydrolysis in THF/hydrochloric
acid at r.t. for 2 h. b Isolated yield. c No hydrolysis.
Experimental
General experimental section
All chemicals were commercially available. All anhydrous solvents
used in the reactions were dried and freshly distilled. Progresses of
reactions were monitored by Thin Layer Chromatography on silica
HSGF254 plates while purification was performed using silica gel
column chromatography. Melting points were recorded on an
electrothermal digital melting point apparatus and are uncorrected.
1H and 13C NMR spectra were obtained from a solution in CDCl3or
d6ꢀDMSO with TMS as internal standard using a 400/101 MHz
(1H/13C) spectrometer. Chemical shifts (δ) are given in ppm and J in
Hz. High resolution mass spectra were carried out on a chemical
ionization (CI) apparatus using timeꢀofꢀflight (TOF) mass
spectrometry.
Scheme2. Examples of forming CꢀO bond
We tried to get compound 3C-a from 3C with the assistance of
hydrochloric acid or Lewis acid (AlCl3, FeCl3 or BF3·Et2O), but the
desired product was not obtained, which might result from the
decomposition of compound 3C. Compound 3C (1 mmol) was
coupled with hydrazine (3 mmol) in refluxing ethanol (10 mL) for 2
hours and the product 3C-b was afforded in 88% yield. Compound
3C-b was the prodrug of tyrosine kinase inhibitor 3ꢀ(pꢀ
tolyl)indeno[1,2ꢀc]pyrazolꢀ4(2H)ꢀone.16ꢀ17 The biology activity
evaluation of Compound 3C-b is underway in our laboratory.
Typical experimental procedure
In a 15 mL sealed tube equipped with a magnetic stirring bar were
added the substrate (1.0 mmol) and LiOtBu (240 mg, 3.0 mmol) in
anhydrous dioxane (2.0 mL) at 60 °C for 0.5 h; Then PdCl2(PPh3)2
(22 mg, 0.05 mmol) and tertꢀbutyl isocyanide (135 ꢁL, 1.2 mmol)
were added; The tube was purged with N2, and the contents were
stirred at 120 °C for another 2 h; After completion of the reaction as
indicated by TLC, the mixture was filtered through neutral
aluminum oxide and the solvent was removed under vacuum.{Then,
the residue was stirred in THF (8 mL) and hydrochloric acid (3 M, 3
Scheme3. Synthesis of the indenopyrazole derivative 3C-b
4 | J. Name., 2012, 00, 1-3
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(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(furan-2-yl)methanone
(3j).Yellow solid (224 mg, 76%); m.p.: 133ꢀ135 °C; 1H NMR (400 MHz,
CDCl3) δ 7.64ꢀ7.66 (m, 2H), 7.59 (s, 1H), 7.52ꢀ7.55(m, 1H), 7.47ꢀ7.54 (m,
2H), 7.21 (d, J = 2.0 Hz, 1H), 6.57(s, 1H), 6.53(s, 1H), 5.68 (s, 1H), 1.39(s,
9H); 13C NMR (100 MHz, CDCl3) δ 184.7, 176.6, 168.4, 150.4, 146.5, 137.6,
134.2, 131.0, 129.6, 128.3, 128.2, 116.4,112.7, 96.7, 52.1, 28.5; HRMSꢀCI
(m/z) calcd. for C18H20NO4[M+H3O]+ : 314.1392; found: 314.1380.
mL) at r.t. for 2 h. The mixture was extracted with EtOAc, dried
with Na2SO4 and evaporated.)}21 The residue was purified on a silica
gel column using petroleum ether/EtOAc as the eluent to give the
pure target product.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(phenyl)methanone(3a).
Yellow solid (256 mg, 84%); m.p.: 139ꢀ141 °C; 1H NMR (400 MHz, CDCl3)
δ 13.13(s, 1H), 7.91 (d, J = 4.0Hz, 1H), 7.71 (d, J = 4.0Hz, 1H), 7.65ꢀ7.67(m,
2H), 7.54ꢀ7.63(m, 2H), 7.40ꢀ7.49 (m, 3H), 1.77(s, 9H); 13C NMR (100 MHz,
CDCl3) δ 192.4, 186.4, 173.0, 140.1, 138.8, 133.5, 132.6, 131.6, 130.8,
128.6, 127.5, 126.9, 123.0, 104.8, 54.6, 30.5; HRMSꢀCI (m/z) calcd. for
C20H20NO2[M+H]+ : 306.1494; found: 306.1495.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(thiophen-2-yl)
methanone (3k).Yellow solid (224 mg, 72%); m.p.: 120ꢀ122 °C; H NMR
1
(400 MHz, CDCl3) δ 7.74 (d, J = 2.0 Hz, 1H), 7.64(d, J = 4.0 Hz, 2H), 7.48ꢀ
7.55 (m, 2H), 7.13ꢀ7.15 (m, 1H), 6.50 (s, 1H), 5.67 (s, 1H),1.38 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 182.2, 181.8, 168.0, 141.0, 137.0, 133.3, 132.6,
130.5, 129.1, 127.9, 127.8, 127.6, 96.8, 51.6, 28.1; HRMSꢀCI (m/z) calcd. for
C18H20NO3S [M+H3O]+ : 330.1164; found:330.1154.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(cyclohexyl)methanone
(3l).Yellow solid (165mg, 53%); m.p.: 141ꢀ142 °C; 1H NMR (400 MHz,
CDCl3) δ 7.51ꢀ7.54(m, 2H), 7.42ꢀ7.47 (m, 2H), 5.93 (s, 1H), 2.24ꢀ2.28 (m,
1H), 1.90 (d, J = 4.0 Hz, 2H), 1.80 (d, J = 4.0 Hz, 2H), 1.69 (d, J = 4.0 Hz,
1H), 1.44(s, 1H), 1.41(s, 9H), 1.20ꢀ1.32 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 198.4, 187.7, 168.4,137.2, 135.2, 130.6, 129.5, 128.1, 128.0, 98.5,
52.0, 46.8, 29.5, 28.6, 25.8, 25.7; HRMSꢀCI (m/z) calcd. for
C20H28NO3[M+H3O]+ : 330.2069; found: 330.2063.
1-(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)-2,2-dimethylpropan-
1-one(3m).Yellow solid (194 mg, 68%); m.p.: 142ꢀ143 °C; 1H NMR (400
MHz, CDCl3) δ 7.51ꢀ7.54(m, 2H), 7.44ꢀ7.49 (m, 2H), 6.04 (s, 1H), 1.41(s,
9H), 1.21(s, 9H); 13C NMR (100 MHz, CDCl3) δ 201.5, 188.3, 168.3, 137.2,
135.5, 130.6, 129.6, 128.1, 128.0, 96.2, 52.0, 39.5, 28.6, 27.3; HRMSꢀCI
(m/z) calcd. for C18H24NO2[M+H]+ :286.1807; found: 286.1801.
ethyl 1-(tert-butylimino)-3-hydroxy-1H-indene-2-carboxylate (3n).
Yellow solid (170 mg, 62%); m.p.: 142ꢀ143 °C; 1H NMR (400 MHz, CDCl3)
δ 10.96 (s, 1H), 7.80 (d, J = 4.0 Hz, 1H)，7.68 (d, J = 4.0 Hz, 1H)，7.53 (t,
J = 8.0 Hz, 1H),7.46 (t, J = 8.0 Hz, 1H),4.33(q, J = 8.0 Hz, 2H), 1.70(s, 9H),
1.39 (t, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ186.0, 172.1, 168.3,
138.5, 132.9, 132.8, 131.0, 126.4, 122.5, 95.4, 59.8, 54.2, 30.8, 14.7; HRMSꢀ
CI (m/z) calcd. for C16H20NO3[M+H]+ :274.1443; found: 274.1441.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(4-methoxyphenyl)
1
methanone (3b).Yellow solid (227 mg, 65%); m.p.: 146ꢀ148 °C; H NMR
(400 MHz, CDCl3) δ 7.93 (d, J = 4.0Hz, 2H), 7.47ꢀ7.63 (m, 3H), 6.95 (d, J =
4.0Hz, 2H), 6.58(s, 1H),5.74(s, 1H), 3.87(s, 3H), 1.37(s, 9H); 13C NMR (100
MHz, CDCl3) δ 187.0, 184.9, 163.5, 137.3, 135.3, 133.4, 132.6, 131.5, 130.7,
129.6, 129.5, 128.2, 128.1, 127.2, 114.0, 96.5, 55.6, 52.0, 28.6; HRMSꢀCI
(m/z) calcd. for C21H22NO3[M+H]+ : 336.1600; found: 336.1581.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(p-tolyl)methanone (3c).
Yellow solid (217 mg, 68%); m.p.: 121ꢀ123 °C; 1H NMR (400 MHz, CDCl3)
δ 7.84 (d, J = 4.0Hz, 2H), 7.63ꢀ7.65 (m, 1H), 7.55ꢀ7.56 (m, 1H), 7.48ꢀ7.50
(m, 2H), 7.25ꢀ7.27 (m, 1H), 6.61 (s, 1H), 5.70 (s, 1H), 2.41 (s, 3H), 1.37(s,
9H); 13C NMR (100 MHz, CDCl3) δ188.4, 184.6,168.5, 143.6, 137.6, 135.5,
131.9, 130.8, 129.7, 129.5, 128.7, 128.2, 128.1, 127.3, 96.7, 52.1, 28.5,
21.8(CH3); HRMSꢀCI (m/z) calcd. for C21H22NO2[M+H]+ : 320.1651; found:
320.1635.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(4-fluorophenyl)
methanone (3d).Yellow solid (229 mg, 71%); m.p.: 144ꢀ146 °C;1H NMR
(400 MHz, CDCl3) δ 7.94ꢀ7.98 (m, 2H), 7.64ꢀ7.66 (m, 1H), 7.48ꢀ7.53 (m,
3H), 7.14 (t, J = 4.0 Hz, 1H), 6.60 (s, 1H), 5.68 (s, 1H), 1.37 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 188.3, 183.8,168.7,167.2, 137.6, 135.3, 131.2,
129.9, 129.8,129.7, 128.3, 128.2, 116.1, 97.1, 52.3, 28.7; HRMSꢀCI (m/z)
calcd. for C20H19FNO2[M+H]+ : 324.1400; found: 324.1386.
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(3-chlorophenyl)
1
methanone (3e).Yellow solid (214 mg, 63%); m.p.: 128ꢀ130 °C; H NMR
(1-(tert-butylimino)-3-hydroxy-5-methoxy-1H-inden-2-yl)(phenyl)
(400 MHz, CDCl3) δ 7.92ꢀ7.93 (m, 1H), 7.80 (d, J = 4.0 Hz, 1H), 7.65ꢀ
7.67(m, 1H), 7.50ꢀ7.54 (m, 3H), 7.40 (t, J = 8.0 Hz, 1H), 6.61 (s, 1H), 5.68
(s, 1H), 1.39(s, 9H); 13C NMR (100 MHz, CDCl3) δ 189.4, 182.4,168.5,
137.6, 136.5, 135.3, 135.0, 132.5, 131.2, 130.0, 129.7, 128.2, 128.1, 127.3,
125.3, 97.3, 52.2, 28.6; HRMSꢀCI (m/z) calcd. for C20H19ClNO2[M+H]+ :
340.1101; found: 340.1105.
1
methanone (3o).Yellow solid (188 mg, 56%); m.p.: 148ꢀ150 °C; H NMR
(400 MHz, CDCl3) δ 13.05(s, 1H), 7.80 (d, J = 4.0Hz, 1H), 7.65ꢀ7.67(m, 2H),
7.40ꢀ7.46(m, 3H), 7.24 (d, J = 2.0 Hz, 1H)，6.98ꢀ7.01 (m, 1H), 3.90(s, 3H),
1.74(s, 9H); 13C NMR (100 MHz, CDCl3) δ 191.8, 185.8, 164.3, 142.5,
140.2, 130.6, 128.7, 128.6, 127.5,123.8, 117.2, 107.9, 104.8, 56.0, 54.4, 30.3;
HRMSꢀCI (m/z) calcd. for C21H22NO3[M+H]+ : 336.1600; found: 336.1604.
(1-(tert-butylimino)-5-fluoro-3-hydroxy-1H-inden-2-yl)(phenyl)
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(4-chlorophenyl)
methanone (3f).Yellow solid (207 mg, 61%); m.p.: 124ꢀ126 °C; 1H NMR
(400 MHz, CDCl3) δ 7.88 (d, J = 4.0 Hz, 2H), 7.64ꢀ7.66(m, 1H), 7.49ꢀ7.53
1
(m, 2H), 7.45 (s, 1H), 7.42 (s, 1H), 6.62(s,1H), 5.67 (s, 1H), 1.38(s, 9H); 13
C
methanone (3p).Yellow solid (174 mg, 54%); m.p.: 142ꢀ144 °C; H NMR
(400 MHz, CDCl3) δ 7.93ꢀ7.95 (m, 2H), 7.54ꢀ7.59 (m, 2H), 7.47 (t, J = 8.0
Hz, 2H), 7.33 (t, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 1H)，6.62(s, 1H),
1.37(s, 9H); 13C NMR (100 MHz, CDCl3) δ 187.9, 184.5, 172.9, 167.6,
164.2, 161.7, 138.0, 134.4, 133.6, 133.1, 130.6, 128.9, 127.5, 117.9, 115.2,
97.3, 52.3, 28.7; HRMSꢀCI (m/z) calcd. for C20H18FNO2[M+H]+ : 323.1322;
found: 323.1325.
NMR (100 MHz, CDCl3) δ 188.9, 182.9,168.6, 139.0, 137.5, 135.3, 133.1,
129.7, 129.1, 128.6, 128.2, 128.1, 97.1, 52.1, 28.5; HRMSꢀCI (m/z) calcd. for
C20H19ClNO2[M+H]+ : 340.1101; found: 340.1098.
benzo[d][1,3]dioxol-5-yl(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)
1
methanone (3g).Yellow solid (264 mg, 72%); m.p.: 148ꢀ150 °C; H NMR
(400 MHz, CDCl3) δ 7.62ꢀ7.64 (m, 1H), 7.53ꢀ7.56(m, 2H), 7.47ꢀ7.50(m, 1H),
7.42 (d, J = 2.0Hz, 1H), 6.86 (d, J = 4.0Hz, 1H), 6.53 (s, 1H), 6.05 (s, 2H),
5.69 (s, 1H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 186.7, 184.9,
168.6, 151.8, 148.4, 137.5, 135.2, 130.9, 129.8, 129.4, 128.2, 123.5,
108.4,107.4, 102.0, 96.8, 52.2, 28.7; HRMSꢀCI (m/z) calcd. for
C21H22NO5[M+H3O]+ : 368.1498; found: 368.1509.
(4-(benzyloxy)phenyl)(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)
methanone(3h).Yellow solid (283 mg, 69%); m.p.: 156ꢀ158 °C; 1H NMR
(400 MHz, CDCl3) δ 7.93(d, J = 4.0Hz, 2H), 7.63ꢀ7.65 (m, 1H), 7.53ꢀ7.56(m,
2H), 7.55ꢀ7.57(m, 1H), 7.35ꢀ7.50(m, 6H), 7.03(d, J = 4.0Hz, 2H), 6.58 (s,
1H), 5.71 (s, 1H), 5.13 (s, 2H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
187.1, 184.7, 168.6, 162.6, 137.3, 136.2, 135.3, 130.8, 129.6, 129.5, 128.7,
128.3, 128.1, 127.6, 127.5, 114.9, 96.5, 70.2(OCH2), 52.1, 28.6; HRMSꢀCI
(m/z) calcd. for C27H26NO3[M+H]+ : 412.1913; found: 412.1910.
2-phenyl-1H-indene-1,3(2H)-dione (4a).22Yellow solid (147 mg, 66%);
m.p.: 165ꢀ167 °C;1H NMR (400 MHz, CDCl3) δ 8.07ꢀ8.09 (m, 2H), 7.90ꢀ
7.93 (m, 2H), 7.31ꢀ7.38 (m, 3H), 7.18ꢀ7.20 (m, 2H), 4.27(s, 1H); 13C NMR
(100 MHz, CDCl3) δ 198.3,142.6,136.0,133.0, 129.0, 128.7, 127.8, 123.7,
59.8; HRMSꢀCI (m/z) calcd. for C15H11O2[M+H]+ : 223.0759; found:
223.0763.
2-(p-tolyl)-1H-indene-1,3(2H)-dione (4b).22Yellow solid (177mg, 75%);
1
m.p.: 142ꢀ144 °C; H NMR (400 MHz, CDCl3) δ 8.05ꢀ8.07 (m, 2H), 7.88ꢀ
7.91 (m, 2H), 7.16 (d, J = 4.0 Hz, 2H), 7.07 (d, J = 4.0 Hz, 2H), 4.18(s, 1H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 198.5, 142.7, 137.6,135.9,
130.2, 129.7, 128.6, 123.7, 65.9, 21.1; HRMSꢀCI (m/z) calcd. for
C16H12O2[M+H]+ : 237.0916; found:237.0919.
2-(3,5-dimethylphenyl)-1H-indene-1,3(2H)-dione(4c).Yellow solid (183
1
mg, 73%); m.p.: 271ꢀ273 °C; H NMR (400 MHz, CDCl3) δ 7.87ꢀ7.89 (m,
(1-(tert-butylimino)-3-hydroxy-1H-inden-2-yl)(naphthalen-2-yl)
2H), 7.72ꢀ7.74 (m, 2H), 6.97(s, 1H), 6.76(s,2H), 2.24(s, 6H); 13C NMR (100
methanone (3i). Yellow solid (305 mg, 86%); m.p.: 235ꢀ237°C; 1H NMR
(400 MHz, CDCl3) δ 13.21(s, 1H), 8.22 (s, 1H, ), 7.92 (d, J = 4.0Hz, 2H),
MHz, CDCl3) δ 197.6, 141.2, 136.9,135.6, 130.4, 130.1, 128.4, 123.9, 64.9,
21.5;HRMSꢀCI (m/z) calcd. for C17H15O2[M+H]+
251.1077.
: 251.1072; found:
7.86 (d, J = 4.0Hz, 2H), 7.72ꢀ7.77(m, 2H), 7.46ꢀ7.63(m, 4H), 1.78(s, 9H); 13
C
NMR (100 MHz, CDCl3) δ 192.2, 186.4, 173.0, 138.8, 137.5, 134.8, 133.5,
132.6, 132.5, 131.7, 129.4, 129.2, 127.8, 127.1, 126.9, 126.8, 126.0, 125.8,
123.0, 105.0, 54.6, 30.5; HRMSꢀCI (m/z) calcd. for C24H22NO2[M+H]+ :
356.1651; found: 356.1629.
2-(4-fluorophenyl)-1H-indene-1,3(2H)-dione (4d).Yellow solid (149mg,
1
62%); m.p.: 248ꢀ250 °C; H NMR (400 MHz, CDCl3) δ 7.89ꢀ7.91 (m, 2H),
7.77ꢀ7.79 (m, 2H), 7.14ꢀ7.18 (m, 2H), 6.93ꢀ6.97 (m, 2H); 13C NMR (100
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

Organic & Biomolecular Chemistry
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VJieowuArrtnicalelONnlainme e
ARTICLE
DOI: 10.1039/C5OB00472A
MHz, CDCl3) δ 197.5, 163.3, 141.0, 136.0, 132.4, 125.4, 124.0, 114.7, 63.5; Electronic Supplementary Information (ESI) available: NMR copies of the
HRMSꢀCI (m/z) calcd. for C15H10O2F [M+H]+ : 241.0665; found: 241.0672.
target products are provided.
22
2-(4-chlorophenyl)-1H-indene-1,3(2H)-dione(4e).
Yellow solid (146
1
mg, 61%); m.p.: 244ꢀ246 °C; H NMR (400 MHz, CDCl3) δ 7.89ꢀ7.91 (m,
2H), 7.77ꢀ7.79 (m, 2H), 7.26ꢀ7.32 (m, 2H), 7.11ꢀ7.13 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 197.7, 163.1, 141.2, 136.4, 132.2, 125.1, 124.5, 114.3,
63.7; HRMSꢀCI (m/z) calcd. for C15H10O2Cl [M+H]+ : 257.0369; found:
257.0360.
1 (a) M. Passerini and L. Simone. Gazz. Chim. Ital., 1921, 51, 126; (b) M.
Passerini and G. Ragni, Gazz. Chim. Ital., 1931, 61, 964.
2 (a) I. Ugi, R. Meyr, U. Fetzer and C. Steinbruckner, Angew. Chem., 1959,
71, 386; (b) I. Ugi and C. Steinbruckner, Angew. Chem., 1960, 72, 267;
(c) I. Ugi, Angew. Chem., Int. Ed. Engl. , 1962, 1, 8.
1H-indene-1,3(2H)-dione (4f).Yellow solid (111 mg, 76%); m.p.: 125ꢀ
1
127 °C; H NMR (400 MHz, CDCl3) δ7.98ꢀ8.00 (s, 2H), 7.84ꢀ7.86 (s, 2H),
3.26 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 197.6, 143.7, 135.8, 124.3,
45.2; HRMSꢀCI (m/z) calcd. for C9H7O2 [M+H]+ : 147.0446; found:
147.0447.
3 (a) T. Nanjo, C. Tsukano and Y. Takemoto, Org. Lett., 2012, 14, 4270;
(b) Z. Xia and Q. Zhu, Org. Lett., 2013, 15, 4110; (c) W. X. Zhang, M.
Nishiura and Z. Hou, Angew. Chem. Int. Ed., 2008, 47, 9700; (d) M.
Tobisu, S. Imoto, S. Ito and N. Chatani, J. Org. Chem. , 2010, 75, 4835;
(e) Z. Hu, D. Liang, J. Zhao, J. Huang and Q. Zhu, Chem. Commun., 2012,
48, 7371; (f) H. Jiang, B. Liu, Y. Li, A.Wang and H. Huang, Org. Lett.,
2011, 13, 1028. (g)Y. Wang and Q. Zhu, Adv. Synth. Catal., 2012, 354,
1902. (h) J. L. Peng, L.Y. Liu, Z.W. Hu, J. B. Huang and Q. Zhu, Chem.
Commun., 2012, 48, 3772. (i) T.H. Zhu, S.Y. Wang, G.N. Wang and S. J.
Ji, Chem. Eur. J., 2013, 19, 5850. (j) S. Lang, Chem. Soc. Rev., 2013, 42,
4867. (k) T. Vlaar, E. Ruijter, B.U.W. Maes and R.V.A. Orru, Angew.
Chem. Int. Ed., 2013, 52, 7084; (l) G.Y.S.Qiu, Q.P.Ding and J. Wu., Chem.
Soc. Rev., 2013, 42,5257.
2-octyl-1H-indene-1,3(2H)-dione (4g).Yellow solid (162 mg, 63%); m.p.:
148ꢀ150 °C; 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 2H), 7.84 (s, 2H), 3.00 (s,
1H), 1.94 (brs, 2H), 1.21ꢀ1.37 (m, 11H), 0.85(brs, 3H); 13C NMR (100 MHz,
CDCl3) δ 201.4, 142.6, 135.7, 123.2, 53.6, 32.0, 29.8, 29.6, 29.4, 27.4, 26.5,
22.8, 14.2; HRMSꢀCI (m/z) calcd. for C17H23O2[M+H]+ : 259.1698; found:
259.1703.
1-(tert-butylimino)-3-oxo-2,3-dihydro-1H-indene-2-carbonitrile(4h).
Yellow solid (138 mg, 61%); m.p.: 153ꢀ155 °C; 1H NMR (400 MHz, CDCl3)
δ 7.64ꢀ7.66 (m, 1H), 7.50ꢀ7.56 (m, 2H), 7.37ꢀ7.39 (m, 1H), 6.34(s, 1H),
1.69(s, 9H); 13C NMR (100 MHz, d6ꢀDMSO) δ 189.6, 162.8, 137.3, 132.5,
132.4, 132.3, 121.7, 120.9, 118.6, 75.6, 55.0, 29.6; HRMSꢀCI(m/z) calcd. for
C14H15N2O [M+H]+ :227.1184; found: 227.1181.
N-(3-cyclohexylideneisobenzofuran-1(3H)-ylidene)-2-methylpropan-2-
amine (4i). White solid (199 mg,74%); m.p.: 82ꢀ84 °C ; 1H NMR (400 MHz,
CDCl3) δ 7.86 (d, J=4.0Hz, 1H), 7.76 (d, J = 4.0Hz, 1H), 7.46(t, J =
8.0Hz,1H), 7.34(t, J = 8.0Hz, 1H), 2.66(t, J = 4.0Hz,2H), 2.59(t, J =
4.0Hz,2H), 1.66ꢀ1.70(m, 6H), 1.45(s, 9H); 13C NMR (100 MHz, CDCl3) δ
152.6, 142.0, 135.6,132.7, 131.1, 127.8, 123.5, 122.3, 120.6, 53.9, 29.4,28.0,
27.6, 27.3, 26.4; HRMSꢀCI (m/z) calcd. for C18H23NO[M]+ : 269.1780;
found: 269.1770.
4 (a) M. Li, X. L. Lv, L. R. Wen and Z.Q. Hu, Org. Lett., 2013,15, 1262; (b)
A. Domling and I. Ugi, Angew. Chem. Int. Ed., 2000, 39, 3168; (c) M. C.
Pirrung and K. D. Sarma, Tetrahedron, 2005, 61, 11456; (d) S.X. Wang,
M.X. Wang, D. X.Wang and J. Zhu, Angew. Chem. Int. Ed., 2008, 47, 388;
(e) S. K1ossowski, B. Wiraszka, S. Ber1o_zecki and R. Ostaszewski, Org.
Lett., 2013, 15, 566; (f) P. R. Andreana, C. C. Liu and S. L. Schreiber,
Org. Lett., 2004, 6, 4231; (g) U. Kusebauch, B. Beck, K. Messer, E.
Herdtweck and A. Domling, Org. Lett., 2003, 5, 4021.
3-methyl-1H-isochromen-1-one (5a).23 White solid (115 mg,72%);
1
m.p.:73ꢀ75 °C; H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 4.0Hz, 1H), 7.67
(t, J = 8.0Hz, 1H), 7.45(t, J = 8.0Hz,1H), 7.34(d, J = 4.0Hz, 1H), 6.26(s, 1H),
2.29(s, 3H); 13C NMR (100 MHz, CDCl3) δ 162.5, 154.1, 137.2, 134.3, 129.0,
127.1, 124.4, 119.4, 103.0, 19.3; HRMSꢀCI (m/z) calcd. for C10H8O2[M]+ :
160.0524; found: 160.0528.
5 X. D. Fei, Z.Y.Ge, T. Tang, Y. M. Zhu and S. J. Ji, J. Org. Chem., 2012,
77, 10321.
2-phenyl-4H-chromen-4-one(B).11 Yellow solid (191 mg, 86%); m.p.: 98ꢀ
1
100 °C; H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 4.0Hz, 1H), 7.93 (d, J =
6 X. Jiang, T. Tang, J. M. Wang, Z. Chen, Y. M. Zhu and S. J. Ji, J. Org.
Chem. , 2014, 79, 5082.
4.0Hz, 2H), 7.71(t, J = 8.0Hz,1H), 7.57(d, J = 4.0Hz, 1H), 7.50ꢀ7.54 (m, 3H),
7.42(t, J = 4.0Hz,1H), 6.85(s, 1H); 13C NMR (100 MHz, CDCl3) δ
178.6,163.6, 156.4, 133.9, 131.9, 131.8, 129.2, 126.4, 125.8, 125.4, 124.1,
118.2, 107.7; HRMSꢀCI (m/z) calcd. for C15H11O2[M+H]+ : 223.0759; found:
223.0755.
2-methyl-N-(3-(p-tolyl)indeno[1,2-c]pyrazol-4(2H)-ylidene)propan-2-
amine (3C-b). Yellow solid (277 mg, 88%); m.p.: 185ꢀ187 °C; 1H NMR
(400 MHz, d6ꢀDMSO) δ 13.2 (d, J = 4.0 Hz, 1H)，7.86ꢀ7.89(m, 1H), 7.60ꢀ
7.64 (m, 2H), 7.24ꢀ7.49 (m, 5H), 6.82(s, 1H), 2.33(s, 3H),1.32(s, 9H,
CH3×3); 13C NMR (100 MHz, CDCl3) δ 169.4, 138.1, 131.2, 130.1, 129.8,
129.2, 128.9,128.3, 128.1, 127.5, 127.0, 125.2, 101.7, 51.1, 29.0, 21.1;
HRMSꢀCI (m/z) calcd. for C21H23N3O [M+H2O]+ :333.1841; found:
333.1847.
7
T.Tang, X. Jiang, J. M. Wang, Y. X. Sun and Y.M. Zhu, Tetrahedron,
2014, 70, 2999.
8 T. Tang, X. D. Fei, Z. Y. Ge, Z. Chen, Y. M. Zhu, and S. J. Ji., J. Org.
Chem., 2013,78, 3170.
9 Z. Chen, H. Q. Duan, X. Jiang, J. M. Wang, Y. M. Zhu and S. L.Yang,
Synlett, 2014, 25, 1425.
10 X. Jiang, J. M. Wang, Y. Zhang, Z. Chen, Y. M. Zhu and S. J. Ji., Org.
Lett., 2014, 16, 3492.
11 J. Zhao, Y. F. Zhao and H. Fu, Angew. Chem. Int. Ed. , 2011, 50, 3769.
12 (a) B. M. Partridge, J. S. Gonzalez and H. W. Lam, Angew. Chem. Int.
Ed.,2014, 53, 6523; (b) G. J. Chuang, W.Wang, E. Lee and T. Ritter, J.
Am. Chem. Soc., 2011, 133, 1760; (c) S. P. Schroder, N. J. Taylor, P.
Jackson and V. Franckevicius, Org. Lett., 2013,15, 3778; (d) S. Gruber
and P.S. Pregosin, Advan. Synth. Catal., 2009, 351, 3235; (e) H. S. Elꢀ
Sheshtawy and A. M. A. Baker, J. Mol. Struc., 2014,1067, 225; (f) S. S.
Dhareshwar and V.J. Stella, J. Pharm. Scien., 2010, 99, 2711; (g) T. L.
Lemke, E. Abebe, P. F. Moore and T. J. Carty, J. Pharm. Sci., 1989, 78,
343.
Acknowledgements
We gratefully acknowledge the financial support by PAPD (A
Project Funded by the Priority Academic Program Development of
Jiangsu Higher Education Institutions).
Notes and references
aCollege of Pharmaceutical Science, Soochow University, 199 Renꢀai Road,
Suzhou
215123,
China.
Eꢀmail:
zhuyongming@suda.edu.cn,
yangshilin@suda.edu.cn
bZhang Zhongjing College of Chinese Medicine, Nanyang Institute of
Technology, 80 Changjiang Road, Nanyang 473000, China.
cJiangxi University of Traditional Chinese Medicine, 56 Yangming Road,
Nanchang 330006, China.
13 A. C. Good, J. Liu, B. Hirth, G. Asmussen, Y. Xiang, H. P. Biemann,
K.A. Bishop, T. Fremgen, M. Fitzgerald, T. Gladysheva, A. Jain, K.
Jancsics, M. Metz, A. Papoulis, R. Skerlj, J. D. Stepp and R. R. Wei , J.
Med. Chem., 2012, 55, 2641.
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
View ArticAle ROnTliInCeLE
DOI: 10.1039/C5OB00472A
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