Palladium-catalyzed intramolecular C-H arylation of 2-halo-: N -Boc- N -arylbenzamides for the synthesis of N-H phenanthridinones

Article abstract of DOI:10.1039/c8ra02099j

A palladium catalyzed synthesis of N-H phenanthridinones was developed via C-H arylation. The protocol gives phenanthridinones regioselectively by one-pot reaction without deprotection. It exhibits broad substrate scope and affords targets in up to 95% yields. Importantly, it could be applied for the less reactive o-chlorobenzamides.

Full text of DOI:10.1039/c8ra02099j

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Palladium-catalyzed intramolecular C–H arylation
of 2-halo-N-Boc-N-arylbenzamides for the
synthesis of N–H phenanthridinones†
Cite this: RSC Adv., 2018, 8, 13879
*
Quan-Fang Hu,
Tian-Tao Gao, Yao-Jie Shi, Qian Lei and Luo-Ting Yu
Received 9th March 2018
Accepted 5th April 2018
A palladium catalyzed synthesis of N–H phenanthridinones was developed via C–H arylation. The protocol
gives phenanthridinones regioselectively by one-pot reaction without deprotection. It exhibits broad
substrate scope and affords targets in up to 95% yields. Importantly, it could be applied for the less
reactive o-chlorobenzamides.
DOI: 10.1039/c8ra02099j
rsc.li/rsc-advances
desired product.6a,6b This is possibly resulted from the coordi-
nation of nitrogen to palladium in the presence of the NH free
amide.5e Earlier reported efficient protocols for such analog
Introduction
Palladium-catalyzed direct functionalization of C–H bonds has
become one of the most efficient and environmentally friendly
mild procedures for building carbon–carbon bonds.1 It holds
a special place among various types of palladium-catalyzed
coupling reactions. C–H direct arylation is its typical applica-
tion, which is catalyzed by Pd(0) or Pd(II) with phosphine
ligands operating under a Pd(0)/Pd(II) or Pd(II)/Pd(IV) catalytic
cycle with or without the assistance of base.2 This coupling
strategy has been well developed in terms of regioselectivity and
efficiency; the tolerance of diverse functional groups makes the
C–H arylation particularly versatile for organic synthesis. The
starting materials may be easily achieved and thus this strategy
has been used for building a variety of aromatic and hetero-
aromatic systems.3
were mediated by potassium tert-butoxide7 or photochem-
istry.8,9 However, those procedures are not regioselective with
substituted anilides due to radical cyclization mechanism
(Scheme 1b, radical pathway for synthesis of N–H phenan-
thridinones), limiting application of substrate scopes.7 So based
on those disadvantages researchers reported utilization of
protection groups which could be easily cleaved aer the ring
closure. Sandro Cacchi and co-workers5e developed N-benzyl
derivatives of N-benzoyl-o-iodoanilides which can be converted
Phenanthridinones are important structural units found in
many natural products and pharmaceuticals that exhibit wide
range of biological activities.4 A variety of novel synthetic
approaches have been developed to the synthesis of the phe-
nanthridinone cores and related lactams, most of them are
based on palladium catalyzed biaryl coupling by the regiose-
lective C–H bond activation (Scheme 1a, synthesis of N-alkyl
phenanthridinones).5 Although they are effective for synthesis
of N-alkyl phenanthridinones, the obvious drawbacks were
observed when applied to N–H phenanthridinones.5e,6 Their
scope of substrates is quite limited and high reaction temper-
ature is necessary. To the best of our knowledge, only the yields
with iodo-substituted anilides are reported. Usually a complex
mixture of side-products is observed, decreasing the yield of
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West
China Medical School, Sichuan University and Collaborative Innovation Center,
Chengdu 610041, China. E-mail: yuluot@scu.edu.cn; Fax: +86-28-85164060; Tel:
+86-28-85164063
Scheme
cyclization.
1
Synthesis of phenanthridinones via intramolecular
RSC Adv., 2018, 8, 13879–13890 | 13879
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c8ra02099j
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activation from Boc protected amide). It can be easily scaled up
even with increasing of yield. The reaction was promoted by
Pd(t-Bu3P)2 combining together with KOAc, a convenient,
commercial available catalyst inexpensive, but highly efficient
to produce a broad range of phenanthridinones.
Results and discussion
The synthesis of the amide starting material 4xy for this inves-
tigation is shown in Scheme 2. Ortho-halogen substituted
arylcarboxylic acid was easily converted to acyl chloride, which
reacted with aniline to give amide 3xy. Then under catalytic
amount of DMAP in DCM, 3xy was almost quantitatively con-
verted to 4xy.10
Scheme 2 Synthesis of cyclization substrates.
In our initial investigation to optimize cyclization conditions
of 4xy, we selected 4aa as starting point for screening, which is
briey summarized in Table 1. The C–H direct arylation is
strongly dependent on the catalyst, the solvent and the base.
Firstly we tried most popular coupling catalyst/base system
(entries 1–3),11 but obtained low yields; Pd(OAc)2/Bu3P/Ag2CO3
system12 gave better yield (38%). Aer that, we tried Pd(PCy3)2
under various basic conditions, and found the yield can be
increased to 48% when KOAc was used. Speculating that
different ligand could be used to ne-tune the reaction due to
its electronic and steric particularities,2d we further screened
Pd(t-Bu3P)2 catalyst13 with different bases and nally identied
Pd(t-Bu3P)2/KOAc was the best combination (entry 11, 72%
yield). Other bases with different cation or anion were inferior
(entries 9, 10). When the optimized condition was utilized with
non-Boc protected substrate 3aa (entry 12), the strategy was not
effective, suggesting that unprotected NH completely inhibited
into the corresponding phenanthridinones in good to high
yields, but needed one more deprotection step in TFA. François
Tillequin et al.6d developed Boc as protection and leaving group,
however, one equivalent of Pd catalyst and two equivalents of
phosphine ligands were involved, and only 26% yield was
obtained.
In this account it is important to develop an operationally
simple catalyst system for direct intramolecular arylation
processes exhibiting broad scope for aryl chlorides, bromides,
and iodides. Here we disclosed a palladium catalyzed one pot
C–H activation protocol, cyclization and decarboxylation of N-
Boc protected o-halobenzamides to produce phenanthridinones
directly, which gave good to excellent yields as high as 95%
(Scheme 1c, synthesis of N–H phenanthridinones by C–H
Table 1 Screening of reaction conditionsa
Entry
Catalyst/ligand (mol%)
Base (equiv.)
Subs. conv. (%)
Yieldb (%)
1
2
3
4
Pd(PPh3)4 (5)
K2CO3 (2)
Cs2CO3 (2)
Ag2CO3 (2)
Cs2CO3 (2)
K2CO3
100
100
89
97
98
22
33
38
35
Pd(OAc)2/PCy3$HBF4 (5/10)
Pd(OAc)2/Bu3P (5/10)
Pd(PCy3)2 (5)
5
Pd(PCy3)2 (5)
31
6
7
8
9
10
11
12c
Pd(PCy3)2 (5)
Pd(PCy3)2 (5)
Pd(PCy3)2 (5)
Pd(t-Bu3P)2 (5)
Pd(t-Bu3P)2 (5)
Pd(t-Bu3P)2 (5)
Pd(t-Bu3P)2 (5)
AgOAc (4)
K3PO4 (2)
KOAc (4)
Cs2CO3 (2)
AgOAc (4)
KOAc (4)
KOAc (4)
83
88
89
98
82
100
18
20
11
48
38
23
72
Trace
a
b
Reaction conditions: 4aa (0.5 mmol), Pd catalyst and base in DMA (5 ml) were heated at 120 ꢀC for 90 min under Ar atmosphere. Yield
c
determined by LCMS. 3aa was used as substrate.
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Table 2 Scope of phenanthridinones formationa
Entry
4xy
5xy
Yieldb [%]
1
2
3
4
5
4ab R1 ¼ R2 ¼ R3 ¼ H R4 ¼ OMe
5ab R1 ¼ R2 ¼ R3 ¼ H R4 ¼ OMe
88
81
87
92
89
4db R1 ¼ Me R2 ¼ R3 ¼ H R4 ¼ OMe
4dc R1 ¼ Me R2 ¼ H R3 ¼ Me R4 ¼ OMe
4ec R1 ¼ H R2 ¼ OMe R3 ¼ Me R4 ¼ OMe
4hd R1 ¼ H R2 ¼ F R3 ¼ Cl R4 ¼ OMe
5db R1 ¼ Me R2 ¼ R3 ¼ H R4 ¼ OMe
5dc R1 ¼ Me R2 ¼ H R3 ¼ Me R4 ¼ OMe
5ec R1 ¼ H R2 ¼ OMe R3 ¼ Me R4 ¼ OMe
5hd R1 ¼ H R2 ¼ F R3 ¼ Cl R4 ¼ OMe
6
7
4lb R1 ¼ H R2 ¼ OMe
4lg R1 ¼ Cl R2 ¼ H
5lb R1 ¼ H R2 ¼ OMe
5lg R1 ¼ Cl R2 ¼ H
91/95c
75
8
37d
9
78
10
82
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Table 2 (Contd.)
Entry
4xy
5xy
Yieldb [%]
11
12
13
4af R1 ¼ R2 ¼ H
5af R1 ¼ R2 ¼ H
84/93c
71
61
4df R1 ¼ Me R2 ¼ H
4ef R1 ¼ H R2 ¼ OMe
5df R1 ¼ Me R2 ¼ H
5ef R1 ¼ H R2 ¼ OMe
14
91
15
16
4kc R1 ¼ Me R2 ¼ OMe
4kg R1 ¼Cl R2 ¼ H
5kc R1 ¼ Me R2 ¼ OMe
5kg R1 ¼Cl R2 ¼ H
83/91c
71
17
18
84
85
19
20
4 R1 ¼ H R2 ¼ OMe
4fc R1 ¼ Me R2 ¼ OMe
5 R1 ¼ H R2 ¼ OMe
5fc R1 ¼ Me R2 ¼ OMe
62
58
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Table 2 (Contd.)
Entry
4xy
5xy
Yieldb [%]
21
22
23
4rc Y1 ¼ C Y2 ¼ N X ¼ Br
4sc Y1 ¼ N Y2 ¼ C X ¼ Br
4tc Y1 ¼ N Y2 ¼ C X ¼ I
5rc Y1 ¼ C Y2 ¼ N
5sc Y1 ¼ N Y2 ¼ C
5tc Y1 ¼ N Y2 ¼ C
0
0
0
a
Reaction conditions: 1 mmol of substrate, 4 equiv. of KOAc, and 5% equiv. of Pd (t-Bu3P)2 in 10 ml DMA were heated at 120 ꢀC for 2 h under Ar
atmosphere. b Isolated yield. c Reaction conducted at 20 mmol scale. d Reacted at 135 ꢀC.
the reaction, presumably resulted by coordination of nitrogen
to palladium in the presence of the NH free amide.5e,14
Our above results showed that diverse functional groups,
including F, Cl, CN, OMe, alkyl and a variety of aryl carboxylic
Aer optimization of the reaction condition, we attempted to acids and aryl amines were well tolerated. It leads us to specu-
extend the scope and generality of the intramolecular coupling late the reaction scope is not limited to bromo-substituted acid,
as shown in Table 2. Various aryl acids and aryl amines were but can also be extended to chloro-substituted acid. So we tested
examined. Electron-rich groups (e.g. Me and OMe) either on the the activity of halogens in Table 3. Firstly, we selected the
acid partner or on the aniline partner could smoothly undergo synthesis of 5aa as example (entries 1a to 1c). When iodide and
cyclization-decarboxylation which exclusively provided the bromide were tested, the reaction can be nished at 120 ꢀC,
desired products in 81–92% yields (entries 1–5). Notably, given 77% and 66% yield respectively. When chloride was
naphthyl-based substrates 4lb and 4lg also gave good to excel- utilized, the yield decreased to moderate (45%) and must be
lent yields (75–95%). 4lg gave lower yield due to slight electron conducted at higher temperature. Aer that, we tested electron-
deciency. When this protocol was subjected to strong electron- donating substitutes on either carboxylic moiety or aniline
decient substrate such as cyano group (5jh, entry 8), the yield moiety (entries 2–5) and found yield can be as high as 78%;
reduced sharply. To explore the cyclization position with respect instead electron-withdrawing substitutes were negative to the
to meta-substituted anilines, we tested meta-isopropyl aniline reaction (entry 6, 38% yield). When the reaction was extended to
(entry 9). The reaction gave para and ortho-cyclization mixtures strong electron withdrawing substituents, the yield decreased
(2 : 1); However when tert-butyl analine was tested (entry 10), signicantly even with iodide (entry 9). Chloro-thiophene
only para-cyclization was produced, presumably due to stronger carboxylic acid also delivered the corresponding products
steric hindrance. It was worth noting that the 3-amino thio- without a problem (entries 7, 8). Considering both chlorine and
phene also gave moderate to high yields (61–93%, entries 11– bromine were active as acid partner, we subjected 4uc for the
14), suggesting it's high C–H activation activity and regiose- reaction. Just as we predicted, the reaction turned to be quite
lectivity. NMR conrmed the coupling is at second position. The messy and yielded no desired target (entry 10).
reaction scope is not limited to benzoic acids, thiophene-
Next we examined the effect of catalyst loading to further
carboxylic acids could also go cyclization smoothly (entries optimize the reaction condition. Substrates 4lb and 4af were
15–20) with aniline or aminothiophene. Similar to early Pd- selected as examples which are shown in Table 4. Firstly we
catalyzated protocol,15 we found that pyridine ring was not an tested 4lb, when the catalyst loading increased from 5 mol% to
effective acid partner under our reaction condition (entries 21– 6 mol%, the inuence was insignicant. However, when it was
23). To further evaluation the protocol's scaling up efficiency, reduced to 4 mol%, the starting material remained and the yield
we tested 4lb/4af/4kc as substrates for gram scale synthesis. To was reduced by 13%; and only 60% yield was obtained when
our delight, the yields increased up from 91%/84%/83% to 95%/ decreased further to 3 mol%; the same situation was observed
93%/91% respectively.
with substrate 4af. Based on research below, 5 mol% catalyst
was established as an optimal catalyst loading.
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Table 3 Scope of the reaction with respect to halogen-substituted substratesa
Entry
4xy
5xy
Yieldb [%]
1a
1b
1c
4aa1 X ¼ I
4aa2 X ¼ Br
4aa3 X ¼ Cl
77c
66c
45
2
68
3
45
4
67
5
78
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Table 3 (Contd.)
Entry
4xy
5xy
Yieldb [%]
6
38
7
53
8
51
9
40
10
0
a
Reaction conditions: 1 mmol of substrate, 4 equiv. of KOAc, and 5% equiv. of (t-Bu3P)2Pd in 10 ml DMA were heated at 135 ꢀC for 2 h under Ar
atmosphere. b Isolated yield. c Reacted at 120 ꢀC.
The directly cleavage of Boc was le for investigation for further produced. It leaded us to suspect the stability of Boc on such
exploring of reaction mechanism. We tested another protection conformationally rigid tricyclic system. So we re-protected the
group acetyl and used it for cyclization. However acetyl group is nal target 5ec with Boc again and then heated it in the reaction
extremely unstable and only trace cyclization product was system at same condition without Pd catalyst (Table 5). To our
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Table 4 Effect of catalyst loadinga
delight, 26% 5ec was produced and 69% 6ec remained. This
result revealed that Boc was a fragile spot however just heating
the substrate couldn't result full decomposition. Pd catalyst
should have played a critical role in catalytic cycle for complete
cleavage.
Entry
Substrate
Pd(t-Bu3P)2
Subs. conv. (%)
Yield (%) of 5b
1
2
3
4
5
6
7
4lb
4lb
4lb
4lb
4af
4af
4af
6%
5%
4%
3%
5%
4%
3%
100
100
94
89
100
93
93
91
78
60
84
61
52
Although additional data are needed to establish the mech-
anism, the fact that Pd catalyst loading inuences the reaction
signicantly and the base KOAc gives the best yield, Boc group
is some extend of fragile suggests their critical roles. It leads us
to propose a plausible Pd(0)/Pd(II) catalytic cycle2 (Scheme 3). A
proton abstraction mechanism previously proposed by Echa-
varren and Maseras,16 was found to explain our reaction
outcomes: (1) the anionic ligand KOAc is directly involved in
C–H bond cleaving; (2) the anion ligand must bind to the
catalyst, but not block the catalytic cycle by competitive occu-
pation of vacant coordination sites;17 (3) the arene which
interacts with the catalyst weakly must compete for binding to
the arylpalladium(II) intermediate with the excess anionic
ligand.18 So initially oxidative addition of polarized Ph–Br bond
to the Pd(0) catalyst forms a highly electrophilic arylpalladium
intermediate I,18,19 which exchange with KOAc to produce
intermediate II,18,20 followed by phosphine dissociation.
Secondly Pd(II) interacts with arene at the ortho position of
aniline in a C–H activation manner which forms intermediate
III.20,21 Here HOAc plays a critical role in the stabilized coordi-
nation intermediate.21,22 Next is irreversible deprotonation:
Pd(II) inserts into the C–H bond of the arene to give cyclo-
biarylpalladium intermediate IV,20–22 accompanied by elimina-
tion of HOAc. Under the effect of produced HOAc, Pd
presumably kicks off Boc and coordinates to nitrogen to give
intermediate V, which nally undergoes reductive elimination
to provide the desired product and regenerates the Pd(0)
catalyst.16,20,22
82
a
Reaction conditions: 1 mmol of substate, 4 equiv. of KOAc, Pd catalyst
and 10 ml DMA were heated at 120 ꢀC for 2 h under Ar atmosphere.
b
Isolated yield.
Table 5 Stability testing of 6eca
Entry
Time (min)
5ec (%)b
6ec (%)b
1
2
60
90
13
26
83
69
a
Reaction conditions: 6ec (0.5 mmol), 4 equiv. of KOAc in DMA (5 ml)
were heated at 120 ꢀC. b Determined by LCMS.
Conclusions
In summary, we have developed a palladium catalyzed C–H
arylation method for synthesis of N–H phenanthridinones from
Boc protected diaryl amide. There are four advantages of using
Boc as protection group: (1) the protection stage gives quantitive
yield and just simple workup produces pure product; (2) the
protection group is stable to some extent compared with acetyl
group; (3) the coupling stage directly gives de-protection nal
targets, additional de-proctection is unnecessary; (3) in contrast
to the system of radical pathway without protection reported by
Bhakuni et al., the regioisomer is not a concern, only a single
desired target was obtained. The catalyst Pd(t-Bu3P)2 is
commercial available, inexpensive and the catalyst loading is
reasonable;
a second phosphine ligand is not required
compared to published method.6d This practical and convenient
method can be easily scaled up, applicable for versatile
substrates and produces high yields. Most important of all, it
could be applied for the less reactive o-chlorobenzamides which
Scheme 3 Proposed mechanism for the phenanthridinone synthesis. greatly extend the substrates scope.
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Representative gram scale procedure for synthesis of 5
Experimental
To a three necked 500 ml ask equipped with a thermometer
was added 4lb (9.13 g, 20 mmol, 1 eq.), DMA (200 ml), anhy-
drous KOAc (azeotroped with toluene prior to use) (7.85 g,
80 mmol, 4 eq.), Pd(t-Bu3P)2 (511.05 mg, 1 mmol, 0.05 eq.). The
mixture was heated under argon at 120 ꢀC for 2 h. The mixture
was diluted with H2O (30 ml) to precipitate the product, ltered
and the solid was washed with H2O and ethanol successively.
The crude product was dissolved in DCM/MeOH (5 : 1), ltered
through celite to remove catalyst residue, then concentrated
and re-crystallized from hexane/ethyl acetate to give pure
compound 5lb (5.23 g, 19 mmol, 95% yield).
General experimental details
Unless otherwise noted, all materials were obtained from
commercial suppliers and used without further purication.
The 1H and 13C NMR spectra were recorded on a Bruker Avance
400 spectrometer at 25 ꢀC using DMSO-d6 or CDCl3 as the
solvent. Chemical shis (d) are reported in ppm relative to
Me4Si (internal standard), coupling constants (J) are reported in
hertz, and peak multiplicity are reported as s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet), or br s (broad
singlet). High resolution mass analysis is performed on
a Waters Q-TOF Premier mass spectrometer with electron spray
ionization (ESI). Thin layer chromatography (TLC) was per-
formed on 0.20 mm silica gel F-254 plates (Qingdao Haiyang
Chemical, China). Visualization of TLC was accomplished with
UV light and/or aqueous potassium permanganate or I2 in silica
gel. Column chromatography was performed using silica gel 60
of 300–400 mesh (Qingdao Haiyang Chemical, China).
Phenanthridin-6(5H)-one (5aa). Off-white solid, 129 mg, 66%
1
yield, TLC Rf 0.5 (2 : 1, petroleum ether : EtOAc); H NMR (400
MHz, DMSO-d6): d 11.69 (s, 1H), 8.52 (d, J ¼ 8.0 Hz, 1H), 8.40 (d,
J ¼ 8.0 Hz, 1H), 8.33 (d, J ¼ 7.6 Hz, 1H), 7.86 (t, J ¼ 7.2 Hz, 1H),
7.65 (t, J ¼ 7.4 Hz, 1H), 7.50 (t, J ¼ 7.4 Hz, 1H), 7.38 (d, J ¼ 8.0 Hz,
1H), 7.27 (t, J ¼ 7.4 Hz, 1H). 13C NMR (100 MHz, DMSO-d6):
d 160.8, 136.5, 134.2, 132.8, 129.6, 127.9, 127.5, 125.7, 123.2,
122.6, 122.3, 117.5, 116.1. ESI-HRMS: calculated for C13H9NNaO
[M + Na]+ 218.0576, found 218.0576.
General procedure for synthesis of 4xy10,23
2-Methoxyphenanthridin-6(5H)-one (5ab). Off-white solid,
198 mg, 88% yield, TLC Rf 0.3 (2 : 1, petroleum ether : EtOAc);
1H NMR (400 MHz, CDCl3): d 11.23 (s, 1H), 8.61 (d, J ¼ 7.6 Hz,
1H), 8.26 (d, J ¼ 8.0 Hz, 1H), 7.83–7.79 (m, 1H), 7.68–7.62 (m,
To suspension of 1x (5 mmol) in SOCl2 (5 ml) was added with 2
drops of DMF. The mixture was heated under reux for 3 h. Then
the mixture was concentrated and diluted with DCM and
concentrated, then diluted and concentrated again to give light
brown semi-solid. The residue was dissolved in anhydrous DCM
(10 ml), added dropwise to a mixture of 2y (5 mmol) and Et3N (12.5
mmol) in DCM (10 ml). The resulting suspension was stirred for
another 1 h aer addition nished. The mixture was diluted with
water, washed with 1 N HCl, 2 N NaOH and brine successively. The
organic layer was dried over Na2SO4, ltered and concentrated to
give the crude amide 3xy which was used for next step directly.
To the above crude 3xy was added anhydrous DCM (20 ml),
DMAP (0.05 eq., 0.25 mmol), and Boc2O (1.2 eq., 6 mmol). The
suspension was stirred until the bubbling was not observed
which indication completion of the reaction. TLC showed a less
polar product which was also conrmed by LCMS. The mixture
was concentrated, diluted with hexane and water. Aer stirring
for a couple of minutes a precipitate deposited. The solid was
ltered, washed with water and hexane, dried under vacuum to
give off-white solid 4xy.
2H), 7.38 (d, J ¼ 8.8 Hz, 1H), 7.14–7.11 (m, 1H), 3.93 (s, 3H); 13
C
NMR (100 MHz, DMSO-d6): d 160.3, 154.8, 134.1, 132.5, 130.7,
127.9, 127.5, 125.9, 123.0, 118.3, 117.7, 117.3, 106.2, 55.6; HRMS
(ESI) m/z calcd for C14H11NNaO2 [M + Na]+ 248.0682, found
248.0690.
3-Isopropylphenanthridin-6(5H)-one (5ae-a). Off-white solid,
123 mg 52% yield, TLC Rf 0.5 (2 : 1, petroleum ether : EtOAc);
1H NMR (400 MHz, DMSO-d6): d 11.60 (s, 1H), 8.46 (d, J ¼ 8.0 Hz,
1H), 8.31–8.29 (m, 2H), 7.83 (t, J ¼ 7.6 Hz, 1H), 7.61 (t, J ¼ 7.4 Hz,
1H), 7.23 (s, 1H), 7.17 (d, J ¼ 8.4 Hz, 1H), 2.93–3.00 (m, 1H), 1.25
(d, J ¼ 6.8 Hz, 6H); 13C NMR (100 MHz, DMSO-d6): d 160.9,
150.2, 136.6, 134.3, 132.7, 127.4, 125.3, 123.2, 122.4, 120.9,
115.6, 113.4, 33.3, 23.6; HRMS (ESI) m/z calcd for C16H15NNaO
[M + Na]+ 260.1046, found 260.1033.
1-Isopropylphenanthridin-6(5H)-one (5ae-b). Off-white solid,
62 mg, 26% yield, TLC Rf 0.5 (2 : 1, petroleum ether : EtOAc); 1H
NMR (400 MHz, CDCl3): d 10.37 (s, 1H), 8.56 (d, J ¼ 7.6 Hz, 1H),
8.24 (d, J ¼ 8.0 Hz, 1H), 7.71 (t, J ¼ 7.6 Hz, 1H), 7.55 (t, J ¼ 6.8 Hz,
1H), 7.38 (t, J ¼ 7.8 Hz, 1H), 7.28 (d, J ¼ 7.6 Hz, 1H), 7.11 (d, J ¼
7.6 Hz, 1H), 3.98–3.93 (m, 1H), 1.39 (d, J ¼ 6.8 Hz, 6H); 13C NMR
(100 MHz, DMSO-d6): d 160.4, 147.0, 137.2, 134.4, 131.9, 128.8,
127.6, 127.2, 127.0, 121.0, 116.1, 113.8, 30.0, 24.5; HRMS (ESI)
m/z calcd for C16H15NNaO [M + Na]+ 260.1046, found 260.1046.
Thieno[3,2-c]isoquinolin-5(4H)-one (5af). Off-white solid,
General procedure for synthesis of product 5 (Tables 2 and 3)
To a 50 ml two necked ask equipped with a thermometer was
added 4xy (1 mmol), DMA (10 ml), KOAc (4 eq., 4 mmol), Pd(t-
Bu3P)2 (0.05 mmol, 0.05 eq.). The mixture was heated under
ꢀ
argon at 120–135 C for 2 h. It was diluted with H2O (30 ml),
ltered and the solid was washed with H2O and ethanol
successively. The crude product was dissolved in DCM/MeOH
(5 : 1), ltered through celite to remove catalyst residue, then
concentrated and re-crystallized from hexane/ethyl acetate to
give almost pure compound 5xy.
Most of the nal compound can be puried by crystallization
easily, for those compounds which has good solubility, a short
silica gel column purication is necessary.
1
169 mg, 84% yield, TLC Rf 0.5 (20 : 1, DCM : MeOH); H NMR
(400 MHz, DMSO-d6): d 12.01 (s, 1H), 8.27 (d, J ¼ 7.6 Hz, 1H),
7.79–7.75 (m, 3H), 7.54–7.50 (m, 1H), 7.06 (d, J ¼ 5.2 Hz, 1H);
13C NMR (100 MHz, DMSO-d6): d 161.4, 138.4, 133.1, 133.0,
128.2, 127.7, 126.3, 123.6, 122.4, 117.9, 115.0; HRMS (ESI) m/z
calcd for C11H7NNaOS [M + Na]+ 224.0141, found 224.0137.
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8.4 Hz, 1H), 6.96 (d, J ¼ 5.2 Hz, 1H). 3.86 (s, 3H); 13C NMR (100
MHz, DMSO-d6): d 161.3, 160.2, 138.9, 135.6, 134.0, 127.9, 117.5,
3-tert-Butylphenanthridin-6(5H)-one (5aj). Off-white solid,
206 mg, 82% yield, TLC Rf 0.7 (2 : 1, petroleum ether : EtOAc);
1H NMR (400 MHz, CDCl3): d 10.99 (s, 1H), 8.51 (d, J ¼ 8.0 Hz,
1H), 8.20 (d, J ¼ 8.0 Hz, 1H), 8.17 (d, J ¼ 8.4 Hz, 1H), 7.74–7.69
(m, 1H), 7.54–7.50 (m, 1H), 7.33–7.27 (m, 2H), 1.35 (s, 9H); 13C
NMR (100 MHz, CDCl3): d 163.4, 153.3, 136.0, 135.0, 132.8,
128.2, 127.4, 125.5, 122.6, 121.9, 120.7, 116.2, 113.4, 35.0, 31.2;
HRMS (ESI) m/z calcd for C17H18NO [M + H]+ 252.1383, found
252.1395.
114.6, 114.3, 112.5, 108.9, 55.8; HRMS (ESI) m/z calcd for C12
-
H9NNaO2S [M + Na]+ 254.0246, found 254.0257.
8-Methoxythieno[3,4-c]quinolin-4(5H)-one (5). Brown
1
solid, 143 mg, 62% yield, TLC Rf 0.6 (10 : 1, DCM : MeOH); H
NMR (400 MHz, DMSO-d6): d 11.06 (s, 1H), 8.49–8.47 (m, 2H),
7.66 (d, J ¼ 2.8 Hz, 1H), 7.22 (d, J ¼ 8.8 Hz, 1H), 7.03–7.00 (m,
1H), 3.84 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d 157.7, 154.7,
136.3, 130.9, 130.2, 129.9, 119.6, 117.3, 117.2, 116.1, 107.5, 55.6;
HRMS (ESI) m/z calcd for C12H9NNaO2S [M + Na]+ 254.0246,
found 254.0246.
6-Oxo-5,6-dihydrophenanthridine-2-carbonitrile (5ci). Brow
1
solid, 88 mg, 40% yield, TLC Rf 0.4 (10 : 1, DCM : MeOH); H
NMR (400 MHz, DMSO-d6): d 12.07 (s, 1H), 8.98 (d, J ¼ 1.6 Hz,
1H), 8.65 (d, J ¼ 8.0 Hz, 1H), 8.34–8.32 (m, 1H), 7.93–7.88 (m,
2H), 7.75–7.71 (m, 1H), 7.48 (d, J ¼ 8.4 Hz, 1H); 13C NMR (100
MHz, DMSO-d6): d 160.9, 139.7, 133.2, 132.9, 132.4, 129.0, 128.6,
127.4, 125.7, 123.2, 119.1, 118.2, 117.1, 104.5; HRMS (ESI) m/z
calcd for C14H8N2NaO [M + Na]+ 243.0529, found 243.0516.
2-Methoxy-10-methylphenanthridin-6(5H)-one (5db). Grey
white solid, 194 mg, 81% yield, TLC Rf 0.4 (2 : 1, petroleum
8-Methoxy-6-methylthieno[3,4-c]quinolin-4(5H)-one
(5fc).
Brown solid, 142 mg, 58% yield, TLC Rf 0.7 (10 : 1,
1
DCM : MeOH); H NMR (400 MHz, DMSO-d6): d 10.08 (s, 1H),
8.52 (d, J ¼ 2.0 Hz, 1H), 8.47 (s, 1H), 7.52 (s, 1H), 6.89 (s, 1H),
3.82 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d 158.1,
154.3, 136.6, 130.7, 130.0, 128.5, 125.8, 119.7, 117.5, 117.3,
105.3, 55.4, 17.9; HRMS (ESI) m/z calcd for C13H11NNaO2S [M +
Na]+ 268.0403, found 268.0398.
1
ether : EtOAc); H NMR (400 MHz, DMSO-d6): d 11.59 (s, 1H),
4-Chloro-7-uoro-2-methoxyphenanthridin-6(5H)-one (5hd).
Light grey solid, 247 mg, 89% yield, TLC Rf 0.5 (1 : 1, petroleum
ether : EtOAc); H NMR (400 MHz, DMSO-d6): d 10.50 (s, 1H),
8.32 (d, J ¼ 7.6 Hz, 1H), 7.94 (d, J ¼ 1.6 Hz, 1H), 7.71 (d, J ¼
7.6 Hz, 1H), 7.55 (t, J ¼ 7.8 Hz, 1H), 7.36 (d, J ¼ 8.8 Hz, 1H), 7.19–
7.16 (m, 1H), 3.85 (s, 3H), 2.97 (s, 3H); 13C NMR (100 MHz,
DMSO-d6): d 160.4, 153.8, 136.9, 135.1, 133.0, 131.0, 127.5,
127.3, 126.1, 119.4, 117.1, 116.1, 111.3, 55.3, 25.4; HRMS (ESI)
m/z calcd for C15H13NNaO2 [M + Na]+ 262.0838, found 262.0842.
2-Methoxy-4,10-dimethylphenanthridin-6(5H)-one (5dc). Off
white solid, 220 mg, 87% yield, TLC Rf 0.7 (1 : 1, petroleum
ether : EtOAc); 1H NMR (400 MHz, DMSO-d6): d 8.77 (s, 1H), 8.51
(d, J ¼ 7.6 Hz, 1H), 7.86 (s, 1H), 7.63 (d, J ¼ 6.8 Hz, 1H), 7.50 (t, J
¼ 7.6 Hz, 1H), 6.98 (s, 1H), 3.89 (s, 3H), 2.99 (s, 3H), 2.51 (s, 3H);
13C NMR (100 MHz, DMSO-d6): d 160.9, 153.2, 137.1, 135.1,
133.6, 129.2, 127.4, 127.3, 126.1, 125.2, 119.5, 117.6, 109.2, 55.3,
25.6, 18.2; HRMS (ESI) m/z calcd for C16H15NNaO2 [M + Na]+
276.0995, found 276.1007.
1
8.43 (d, J ¼ 8.0 Hz, 1H), 7.89–7.85 (m, 2H), 7.45 (dd, J ¼ 11.6,
8.4 Hz, 1H), 7.36 (d, J ¼ 2.0 Hz, 1H); 3.89 (s. 3H); 13C NMR was
not obtained due to low solubility; HRMS (ESI) m/z calcd for
C
14H9ClFNNaO2 [M + Na]+ 300.0198, found 300.0208.
Dithieno[3,2-b:30,20-d]pyridin-5(4H)-one (5if). Brown solid,
1
176 mg, 85% yield, TLC Rf 0.6 (10 : 1, DCM : MeOH); H NMR
(400 MHz, DMSO-d6): d 12.23 (s, 1H), 8.17 (d, J ¼ 4.0 Hz, 1H),
7.79 (d, J ¼ 4.8 Hz, 1H), 7.61 (d, J ¼ 4.4 Hz, 1H), 7.11 (d, J ¼
4.4 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d 156.0, 139.9,
135.3, 127.5, 127.1, 122.6, 117.4, 113.3; HRMS (ESI) m/z calcd for
C9H5NNaOS2 [M + Na]+ 229.9705, found 229.9718.
8-Methyl-6-oxo-5,6-dihydrophenanthridine-4-carbonitrile
(5jh). Brown solid, 87 mg, 37% yield, TLC Rf 0.6 (20 : 1,
9-Methylthieno[3,2-c]isoquinolin-5(4H)-one (5df). Brown
1
1
DCM : MeOH); H NMR (400 MHz, CDCl3): d 8.93 (s, 1H), 8.42
solid, 153 mg, 71% yield, TLC Rf 0.7 (10 : 1, DCM : MeOH); H
(d, J ¼ 8.0 Hz, 1H), 8.36 (s, 1H), 8.18 (d, J ¼ 8.0 Hz, 1H), 7.75–
7.68 (m, 2H), 7.36 (t, J ¼ 7.8 Hz, 1H), 2.57 (s, 3H); 13C NMR was
not obtained due to low solubility; HRMS (ESI) m/z calcd for
NMR (400 MHz, DMSO-d6): d 12.10 (s, 1H), 8.25 (d, J ¼ 8.0 Hz,
1H), 7.90 (d, J ¼ 5.2 Hz, 1H), 7.68 (d, J ¼ 7.2 Hz, 1H), 7.44 (t, J ¼
7.6 Hz, 1H), 7.15 (d, J ¼ 5.6 Hz, 1H), 2.75 (s, 3H); 13C NMR (100
MHz, DMSO-d6): d 161.3, 138.2, 134.7, 132.6, 132.1, 128.6, 126.3,
C
15H10N2NaO [M + Na]+ 257.0685, found 257.0696.
8-Methoxy-6-methylthieno[3,2-c]quinolin-4(5H)-one (5kc).
125.6, 124.6, 117.2, 113.9, 22.0; HRMS (ESI) m/z calcd for C12
-
H9NNaOS [M + Na]+ 238.0297, found 238.0318.
Brown solid, 204 mg, 83% yield, TLC Rf 0.7 (10 : 1,
1
DCM : MeOH); H NMR (400 MHz, DMSO-d6): d 10.73 (s, 1H),
2,7-Dimethoxy-4-methylphenanthridin-6(5H)-one (5ec). Off-
white solid, 247 mg, 92% yield, TLC Rf 0.7 (20 : 1,
7.78 (d, J ¼ 5.6 Hz, 1H), 7.60 (d, J ¼ 5.2 Hz, 1H), 7.11 (d, J ¼
2.4 Hz, 1H), 7.01 (d, J ¼ 2.0 Hz, 1H), 3.83 (s, 3H), 2.46 (s, 3H); 13
C
1
DCM : MeOH); H NMR (400 MHz, DMSO-d6): d 10.08 (s, 1H),
NMR (100 MHz, DMSO-d6): d 158.1, 154.1, 145.8, 131.1, 129.0,
126.7, 126.4, 125.3, 119.3, 116.8, 103.1, 55.4, 17.8; HRMS (ESI)
m/z calcd for C13H11NNaO2S [M + Na]+ 268.0403, found
268.0411.
8.06 (d, J ¼ 8.0 Hz, 1H), 7.73 (t, J ¼ 8.2 Hz, 1H), 7.63 (d, J ¼
2.4 Hz, 1H), 7.18 (d, J ¼ 8.4 Hz, 1H), 6.99 (d, J ¼ 2.0 Hz, 1H), 3.89
(s, 3H), 3.84 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, DMSO-d6):
d 160.9, 159.3, 153.9, 137.2, 133.4, 129.7, 125.0, 119.2, 117.8,
114.9, 114.7, 110.8, 104.4, 56.0, 55.5, 17.5; HRMS (ESI) m/z calcd
for C16H16NO3 [M + H]+ 270.1125, found 270.1118.
Dithieno[3,2-b:20,30-d]pyridin-5(4H)-one (5kf). Brown solid,
1
174 mg, 84% yield, TLC Rf 0.6 (10 : 1, DCM : MeOH); H NMR
(400 MHz, DMSO-d6): d 12.15 (s, 1H), 7.79 (d, J ¼ 5.2 Hz, 1H),
7.62 (d, J ¼ 5.2 Hz, 1H), 7.54 (d, J ¼ 4.8 Hz, 1H), 7.09 (d, J ¼
5.2 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d 158.4, 142.1,
139.4, 128.5, 127.6, 125.3, 124.1, 117.6, 112.2; HRMS (ESI) m/z
calcd for C9H6NOS2 [M + H]+ 207.9885, found 207.9880.
6-Methoxythieno[3,2-c]isoquinolin-5(4H)-one (5ef). Brown
solid, 141 mg, 61% yield, TLC Rf 0.7 (10 : 1, DCM : MeOH); H
1
NMR (400 MHz, DMSO-d6): d 11.63 (s, 1H), 7.73 (d, J ¼ 5.2 Hz,
1H), 7.65 (t, J ¼ 8.2 Hz, 1H), 7.25 (d, J ¼ 8.0 Hz, 1H), 7.03 (d, J ¼
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7.35 (m, 3H), 4.02 (s, 3H), 3.10–3.03 (m, 1H), 1.36 (d, J ¼ 6.8 Hz,
6H); 13C NMR (100 MHz, CDCl3): d 159.3, 143.5, 133.1, 128.6,
127.0, 123.8, 122.6, 119.6, 118.5, 116.7, 108.7, 55.7, 34.1, 24.3;
HRMS (ESI) m/z calcd for C17H17NNaO2 [M + Na]+ 290.1151,
found 290.1147.
6-Chlorothieno[3,2-c]quinolin-4(5H)-one (5kg). Brown solid,
167 mg, 71% yield, TLC Rf 0.6 (20 : 1, DCM : MeOH); H NMR
1
(400 MHz, DMSO-d6): d 10.91 (s, 1H), 7.88–7.86 (m, 2H), 7.66–
7.63 (m, 2H), 7.27 (t, J ¼ 7.8 Hz, 1H). 13C NMR (100 MHz, DMSO-
d6): d 157.9, 145.3, 132.5, 131.5, 129.4, 128.0, 125.3, 123.1, 122.6,
119.3, 117.9. ESI-HRMS: calculated for C11H6ClNNaOS [M + Na]+
257.9751, found 257.9739.
3-tert-Butyl-10-methylphenanthridin-6(5H)-one (5nj). Off-
white solid, 207 mg, 78% yield, TLC Rf 0.7 (1 : 1, petroleum
1
ether : EtOAc); H NMR (400 MHz, DMSO-d6): d 11.58 (s, 1H),
2-Methoxybenzo[k]phenanthridin-6(5H)-one (5lb). Off-white
solid, 250 mg, 91% yield, TLC Rf 0.5 (2 : 1, petroleum ether-
: EtOAc); 1H NMR (400 MHz, DMSO-d6): d 11.85 (s, 1H), 9.01 (d,
J ¼ 7.2 Hz, 1H), 8.33 (d, J ¼ 8.8 Hz, 1H), 8.17–8.08 (m, 3H), 7.80–
7.78 (m, 2H), 7.47 (d, J ¼ 8.8 Hz, 1H), 7.28–7.25 (m, 1H), 3.90 (s,
3H); 13C NMR (100 MHz, DMSO-d6): d 160.4, 154.2, 135.7, 132.5,
131.5, 129.0, 128.6, 128.4, 128.1, 127.4, 126.9, 124.9, 122.9,
118.1, 117.4, 117.2, 111.1, 55.5; HRMS (ESI) m/z calcd for
8.39 (d, J ¼ 8.8 Hz, 1H), 8.29 (d, J ¼ 7.2 Hz, 1H), 7.69 (d, J ¼
7.2 Hz, 1H), 7.51 (t, J ¼ 7.6 Hz, 1H), 7.45 (d, J ¼ 1.6 Hz, 1H), 7.32
(dd, J ¼ 8.8, 2.0 Hz, 1H), 2.92 (s, 3H), 1.34 (s, 9H); 13C NMR (100
MHz, DMSO-d6): d 161.0, 151.5, 136.9, 136.8, 134.9, 133.2, 127.1,
126.8, 126.0, 119.3, 116.4, 112.7, 34.4, 30.8, 25.5; HRMS (ESI) m/
z calcd for C18H19NNaO [M + Na]+ 288.1359, found 288.1370.
8-Methoxythieno[3,2-c]quinolin-4(5H)-one (5ob). Brown
1
solid, 123 mg, 53% yield, TLC Rf 0.7 (10 : 1, DCM : MeOH); H
C
18H14NO2 [M + H]+ 276.1019, found 276.1028.
NMR (400 MHz, DMSO-d6): d 11.63 (s, 1H), 7.79 (d, J ¼ 5.2 Hz,
1H), 7.58 (d, J ¼ 5.2 Hz, 1H), 7.36 (d, J ¼ 8.8 Hz, 1H), 7.26 (d, J ¼
2.4 Hz, 1H), 7.14 (dd, J ¼ 8.8, 2.8 Hz, 1H), 3.85 (s, 3H); 13C NMR
(100 MHz, DMSO-d6): d 157.7, 154.6, 145.1, 131.4, 130.4, 126.7,
125.3, 118.2, 117.6, 116.8, 105.2, 55.6; HRMS (ESI) m/z calcd for
Benzo[f]thieno[3,2-c]isoquinolin-5(4H)-one (5lf). Brown
1
solid, 229 mg, 91% yield, TLC Rf 0.7 (20 : 1, DCM : MeOH); H
NMR (400 MHz, DMSO-d6): d 12.55 (s, 1H), 8.89 (d, J ¼ 8.4 Hz,
1H), 8.39 (d, J ¼ 8.8 Hz, 1H), 8.17 (d, J ¼ 7.6 Hz, 1H), 8.04–8.01
(m, 2H), 7.90 (t, J ¼ 7.4 Hz, 1H), 7.83 (t, J ¼ 7.4 Hz, 1H), 7.26 (d, J
¼ 5.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): d 161.2, 140.1,
135.1, 131.8, 129.4, 129.2, 128.4, 127.6, 127.1, 126.8, 125.5,
124.1, 122.1, 117.4, 112.8; HRMS (ESI) m/z calcd for C15H9NNaO
[M + Na]+ 274.0297, found 274.0314.
4-Chlorobenzo[k]phenanthridin-6(5H)-one (5lg). Grey solid,
210 mg, 75% yield, TLC Rf 0.4 (2 : 1, petroleum ether : EtOAc);
1H NMR (400 MHz, DMSO-d6): d 11.08 (s, 1H), 8.89–8.87 (m, 1H),
8.58 (d, J ¼ 8.0 Hz, 1H), 8.33 (d, J ¼ 8.4 Hz, 1H), 8.20–8.15 (m,
2H), 7.83–7.74 (m, 3H), 7.38 (t, J ¼ 8.0 Hz, 1H); 13C NMR (100
MHz, DMSO-d6): d 156.2, 131.3, 128.2, 127.7, 124.3, 123.9, 123.7,
123.1, 122.2, 122.0, 121.9, 119.6, 118.0, 117.0, 115.1, 114.9,
113.6; HRMS (ESI) m/z calcd for C17H11ClNO [M + H]+ 276.1019,
found 276.1026.
2,8-Dimethoxyphenanthridin-6(5H)-one (5mb). Light yellow
solid, 174 mg, 68% yield, TLC Rf 0.4 (1 : 1, petroleum ether-
: EtOAc); 1H NMR (400 MHz, DMSO-d6): d 11.58 (s, 1H), 8.49 (d,
J ¼ 9.2 Hz, 1H), 7.80–7.76 (m, 2H), 7.45–7.42 (m, 1H), 7.28 (d, J ¼
8.8 Hz, 1H), 7.08 (dd, J ¼ 8.8, 2.8 Hz, 1H), 3.92 (s, 3H), 3.86 (s,
3H); 13C NMR (100 MHz, DMSO-d6): d 160.1, 159.0, 154.9, 129.6,
127.5, 127.3, 124.9, 121.3, 118.5, 117.1, 116.5, 108.7, 105.7, 55.6,
55.4; HRMS (ESI) m/z calcd for C15H13NNaO3 [M + Na]+
278.0788, found 278.0797.
C
12H9NNaO2S [M + Na]+ 254.0246, found 254.0252.
8-Isopropylthieno[3,2-c]quinolin-4(5H)-one (5ok). Brown
1
solid, 124 mg, 51% yield, TLC Rf 0.5 (20 : 1, DCM : MeOH); H
NMR (400 MHz, DMSO-d6): d 11.67 (s, 1H), 7.77 (d, J ¼ 5.2 Hz,
1H), 7.63 (d, J ¼ 2.8 Hz, 1H), 7.58 (d, J ¼ 5.2 Hz, 1H), 7.42–7.35
(m, 2H), 3.04–2.97 (m, 1H), 1.26 (d, J ¼ 6.8 Hz, 6H); 13C NMR
(100 MHz, DMSO-d6): d 158.1, 145.6, 142.7, 134.4, 131.1, 127.9,
126.4, 125.3, 120.3, 116.3, 116.1, 32.9, 23.9; HRMS (ESI) m/z
calcd for C14H13NNaOS [M + Na]+ 266.0610, found 266.0641.
4-Fluoro-7-methoxyphenanthridin-6(5H)-one (5pl). Light
yellow solid, 93 mg, 38% yield, TLC Rf 0.5 (1 : 1, petroleum
1
ether : EtOAc); H NMR (400 MHz, DMSO-d6): d 11.12 (s, 1H),
8.14 (d, J ¼ 8.0 Hz, 1H), 8.04 (d, J ¼ 8.0 Hz, 1H), 7.78 (t, J ¼
8.2 Hz, 1H), 7.38–7.34 (m, 1H), 7.24 (d, J ¼ 8.4 Hz, 1H), 7.20–7.15
(m, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d 161.0,
159.0, 150.0, 147.6, 136.4, 133.9, 125.8, 125.7, 121.4, 121.3,
119.5, 114.9, 114.8, 114.7, 111.5, 56.0; HRMS (ESI) m/z calcd for
C
14H10FNNaO2 [M + Na]+ 266.0588, found 266.0599.
Conflicts of interest
There are no conicts of interest to declare.
2,8-Dimethoxy-4-methylphenanthridin-6(5H)-one
(5mc).
Light yellow solid, 180 mg, 67% yield, TLC Rf 0.5 (1 : 1, petro-
leum ether : EtOAc); H NMR (400 MHz, CDCl3): d 8.66 (s, 1H),
Acknowledgements
1
We thank Chengdu ChemPartner Co., Ltd. for technical,
reagents and analysis support. We also thank Lihua Zhou and
Professor Lijuan Chen's team of State Key Laboratory of Bio-
therapy (Sichuan University) for NMR and HRMS
measurements.
8.08 (d, J ¼ 8.8 Hz, 1H), 7.86 (d, J ¼ 2.8 Hz, 1H), 7.40 (d, J ¼
2.4 Hz, 1H), 7.31 (dd, J ¼ 8.8, 2.8 Hz, 1H), 6.84 (d, J ¼ 2.0 Hz,
1H), 3.90 (s, 3H), 3.83 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz,
DMSO-d6): d 160.5, 159.0, 154.3, 128.0, 127.8, 127.0, 125.7,
125.2, 121.7, 118.5, 117.9, 108.4, 103.5, 55.5, 17.7; HRMS (ESI)
m/z calcd for C16H15NNaO3 [M + Na]+ 292.0944, found 292.0954.
2-Isopropyl-8-methoxyphenanthridin-6(5H)-one (5mk). Off-
white solid, 120 mg, 45% yield, TLC Rf 0.6 (1 : 1, petroleum
ether : EtOAc); 1H NMR (400 MHz, CDCl3): d 11.16 (s, 1H), 8.27
(d, J ¼ 9.2 Hz, 1H), 8.03 (d, J ¼ 2.0 Hz, 1H), 7.99 (s, 1H), 7.42–
Notes and references
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´
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