Synthesis of isomeric angularly fused dihydroquinazolinoquinazolinones and an unusual oxidative rearrangement

Article abstract of DOI:10.1016/j.tetlet.2012.10.108

Cyclization of 2-(2-aminophenyl)-2,3-dihydroquinazolin-4(1H)-ones onto N₁-nitrogen and onto N₃-nitrogen leading to 11b,12-dihydro-(13H)-quinazolino[3,4-a]quinazolin-13-ones and 13,13a-dihydro-(8H)-quinazolino[4,3-b]quinazolin-8-ones, respectively, is described for the first time. An unusual dehydrogenative rearrangement of 11b,12-dihydro-(13H)-quinazolino[3,4-a]quinazolin-13-one to (8H)-quinazolino[4, 3-b]quinazolin-8-one is also described.

Full text of DOI:10.1016/j.tetlet.2012.10.108

Tetrahedron Letters 54 (2013) 128–131
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
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Synthesis of isomeric angularly fused dihydroquinazolinoquinazolinones
and an unusual oxidative rearrangement q
⇑
Somepalli Venkateswarlu , Meka Satyanarayana, Kolla Srinivas, Kodumuri N. V. V. Aadisudhakar
Drug Discovery, Laila Impex Research Centre, No. 1, Phase III, Jawahar Autonagar, Vijayawada 520 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclization of 2-(2-aminophenyl)-2,3-dihydroquinazolin-4(1H)-ones onto N1-nitrogen and onto
N3-nitrogen leading to 11b,12-dihydro-(13H)-quinazolino[3,4-a]quinazolin-13-ones and 13,13a-dihy-
dro-(8H)-quinazolino[4,3-b]quinazolin-8-ones, respectively, is described for the first time. An unusual
dehydrogenative rearrangement of 11b,12-dihydro-(13H)-quinazolino[3,4-a]quinazolin-13-one to
(8H)-quinazolino[4,3-b]quinazolin-8-one is also described.
Received 1 September 2012
Revised 6 October 2012
Accepted 9 October 2012
Available online 1 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Fused quinazolinoquinazolinones
Cyclization
Dehydrogenation
DDQ
Rearrangement
Over the past decade, the synthesis of heterocyclic compounds
has become the cornerstone of synthetic organic chemistry as a re-
sult of a wide variety of their application in medicinal and pharma-
ceutical chemistry.1 Exploration of heterocycles as privileged
structures in drug discovery is the important major area in medic-
inal chemistry.2 Quinazolin-4(3H)-one possess many biological
activities3 and their synthesis has been extensively investigated.4
4-Anilinoquinazolines are shown to possess EGFR (epidermal
growth factor receptor) tyrosine kinase inhibitory effects, useful
to inhibit tumor growth.5 For example, IressaÒ and TarcevaÒ are
two selective EGFR-TK inhibitors approved by the FDA in 2004
for locally advanced or metastatic non-small cell lung cancer
(NSCLC) therapy. (8H)-Quinazolino[4,3-b]quinazolin-8-ones (1)
and (13H)-quinazolino[3,4-a]quinazolin-13-ones (2) are two iso-
meric angularly fused quinazolinoquinazolinones. Although there
are a few synthetic methods reported for the synthesis of 16 and
2,7 synthesis of the corresponding dihydro derivatives were not re-
ported in the literature. In view of the important biological activi-
ties of the fused quinazolinones and in continuation of our interest
in this chemistry,8 herein we describe the first synthesis of dihy-
droquinazolinoquinazolinones and an unusual dehydrogenative
rearrangement of 11b,12-dihydro-(13H)-quinazolino[3,4-a]qui-
nazolin-13-one.
Cyclization of 2-(2-aminophenyl)quinazolin-4(3H)-one (3a)
with triethyl orthoformate9 and auto-redox based cyclization of 2-
(2-nitrophenyl)quinazolin-4(3H)-one (3b) with tin (II) chloride in
the presence of alcohols10 onto N3-nitrogen to give (8H)-quinazoli-
no[4,3-b]quinazolin-8-ones (1) and 5,6-dihydro-quinazolino[4,3-
b]quinazolin-8-ones (1a), respectively, via path a, are well estab-
lished (Fig. 1). Recently, we reported the cyclization of 3a with acetic
anhydride onto N3 and onto N1-nitrogen leading to 6-methyl-(8H)-
quinazolino[4,3-b]quinazolin-8-one (1b) and 6-methyl-(13H)-
O
N
N
N
O
a
N
)
3
Patha
t
E
O
NH
b
R
1
3
(
C
H
1
N
R1
P
O
a
t
h
S
a
n
C
3a
: R=NH2
NH
l
2
3b: R=NO2
Ac2O
Path b
N
1a
Path a
O
N
O
CH3
N
N
N
N
N
q
2a
Laila Communication #98.
1b
⇑
Corresponding author. Tel.: +91 866 2546185; fax: +91 866 2546216.
E-mail addresses: somepalli01@rediffmail.com, drvsomepalli@gmail.com
H3C
(S. Venkateswarlu).
Figure 1. Known cyclization of 3 via paths a and b.
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.10.108

S. Venkateswarlu et al. / Tetrahedron Letters 54 (2013) 128–131
129
Table 1
entries 1–6) via path b. However, with dimethylformamide–
dimethylacetal (DMF–DMA), the reaction proceeded competitively
via paths a and b to give the compounds 5a and 6a in good yield
(entries 7 and 9). But with the same reagent under acid catalyst,
the reaction proceeded selectively through path b and gave 6a in
good yield (entry 8). The structures of 5a and 6a have been de-
duced from its spectroscopic data. Next, with the two-carbon
equivalent reagents such as acetic acid and acetic anhydride, the
acetylated products were obtained instead of the products,
whereas with triethyl orthoacetate the reaction proceeded selec-
tively through path b, and gave 6-methyl substituted compound
6f in good yield (entries 13 and 14). These results indicate that
the cyclization onto N1-nitrogen is more favorable to give com-
pound 6, which might be due to better stability (due to the ex-
tended conjugation through amide nitrogen) of the system 6.
Calculations based on PCMODEL indicated that the compound 6a
is substantially more stable than the compound 5a. To the best
of our knowledge this is the first report on the formation of both
the isomeric angular fused dihydroquinazolinoquinazolinones by
the cyclization of 2-(2-aminophenyl)-2,3-dihydroquinazolin-
4(1H)-one.
Encouraged by the above results, the reaction was tried with
various 2-(2-aminophenyl)-2,3-dihydroquinazolin-4(1H)-ones (4)
with DMF–DMA to check the generality of the method for generat-
ing isomeric angularly fused dihydroquinazolinoquinazolinones.
The substituted 4 were obtained from the corresponding 2-amin-
obenzamides and 2-nitrobenzaldehydes as depicted in Scheme 1.
The synthetic methodology commenced with the synthesis of
2,3-dihydro-2-(2-nitrophenyl)quinazolin-4(1H)-ones (7) by reflux-
ing anthranilamide and 2-nitrobenzaldehydes in the presence of
water.11 The nitro functionality was reduced using iron powder
to generate 4, which were reacted with DMF–DMA in toluene to
give two isomeric angularly fused dihydroquinazolinoquinazoli-
nones (5 and 6).12 The two products were separated and character-
ized by their analytical and spectroscopic data.13
Cyclization of 4a with various reagentsa
O
9
6
7
10
11
5
8
N
N
2
13
O
a
4
3
N
13a
12
1
H
a
NH NH2
1
3
h
t
5a
O
a
1
P
N
H
13
b
12
P
2
3
a
NH
t
h
4a
11
b
11b
5
10
9
N
4
6
7
N
R
8
6a, R=H; 6f, R=CH3
Entry
Reagent
Solvent/catalyst/conditions
Yieldb (%)
6a/6f
5a
1
2
3
4
5
6
7
8
HC(OEt)3
HC(OEt)3
HC(OEt)3
HC(OEt)3
HC(OEt)3
HCOOH
Toluene/rt, 16 h
—
—
—
—
—
—
19
—
22
—
—
—
—
—
76
76
76
76
70
70
48
76
51
—
Toluene/reflux, 2 h
HC(OEt)3/reflux, 2 h
Toluene/AcOH/reflux, 2 h
Toluene/TEA/reflux, 2 h
HCOOH/reflux, 2 h
DMF–DMA
DMF–DMA
DMF–DMA
AcOH
Toluene/reflux, 2 h
Toluene/AcOH/reflux, 2 h
Toluene/TEA/reflux, 2 h
AcOH/reflux, 2 h
9
10
11
12
13
14
Ac2O
Ac2O/reflux, 2 h
—
CH3C(OEt)3
CH3C(OEt)3
CH3C(OEt)3
Toluene/reflux, 2 h
Toluene/AcOH/reflux, 2 h
Toluene/TEA/reflux, 2 h
55
73
73
a
All the reactions were performed with 4a (10 mmol), reagent (20 mmol), and
optionally acid or base.
b
Isolated yields.
quinazolino[3,4-a]quinazolin-13-one (2a), respectively.8 However
cyclization of 2-(2-aminophenyl)-2,3-dihydroquinazolin-4(1H)-
one (4a) has not been studied. This prompted us to study this cycli-
zation reaction. The required 4a was obtained from anthranilamide
and 2-nitrobenzaldehyde in two steps.11 Compound 4a was then
treated with various reagents and the results are summarized in Ta-
ble 1.
First, the reaction was examined under one-carbon equivalent
reagents such as triethyl orthoformate and formic acid; the cycliza-
tion went smoothly and selectively to give compound 6a (Table 1,
It was contemplated that the dehydrogenation reaction of 5 and
6 would lead to compounds 1 and 2. Among the several reagents
known,14 DDQ was chosen for the aromatization reaction. Thus,
dehydrogenation of 13,13a-dihydro-(8H)-quinazolino[4,3-b]qui-
nazolin-8-one (5a) with 1.5 equiv of DDQ gave (8H)-quinazoli-
no[4,3-b]quinazolin-8-one (1) in good yield. The structure of 1
has been deduced from its spectroscopic data and confirmed by
comparing with that described in the literature.6c However,
O
R1
R1
R2
CONH2
NH2
R3
R4
CHO
NO2
NH NO2
(i)
O
(ii)
+
R2
N
H
R4
7
R3
O
O
R1
R2
R1
R2
R1
R2
N
N
NH NH2
NH
N
(iii)
+
R3
R4
N
H
N
H
N
R4
R4
4
5
R3
6
R3
(14-22%)
(51-56%)
a: R1=R2=R3=R4=H
b: R1=R2=OCH3, R3=R4=H
c: R1=R2=H, R3=R4=OCH3
d: R1=Cl, R2=H, R3=R4=OCH3
e: R1=Br, R2=H, R3=R4=OCH3
Scheme 1. Reagents and conditions: (i) H2O:AcOH, reflux, 5 h, 71–86% (ii) Fe/HCl, NH4Cl, MeOH, reflux, 0.5 h, 70–92% (iii) DMF–DMA, Et3N, toluene, reflux, 3 h, 68–73%.

130
S. Venkateswarlu et al. / Tetrahedron Letters 54 (2013) 128–131
6a
DDQ, dioxane
more stable, which might be the driving force for the
rearrangement.
The mechanism of the rearrangement is not very clear at this
moment. For simplicity, the carbonium ion based tentative mech-
anism (an analogous free radical based mechanism can also be
visualized) is depicted in Scheme 3.
In summary, we have described an approach for the synthesis of
isomeric angularly fused dihydroquinazolinoquinazolinones. 2-(2-
Aminophenyl)-2,3-dihydroquinazolin-4(1H)-one was cyclized
selectively onto N1-nitrogen to provide 11b,12-dihydro-(13H)-qui-
nazolino[3,4-a]quinazolin-13-one using formic acid, triethyl ortho-
formate, and triethyl orthoacetate. However with DMF–DMA
under neutral or basic conditions, the cyclization is onto N3 and
N1-nitrogen leading to 13,13a-dihydro-(8H)-quinazolino[4,3-b]
quinazolin-8-one and 11b,12-dihydro-(13H)-quinazolino[3,4-a]
quinazolin-13-one, respectively. This methodology provides an en-
try for the isomeric angularly fused dihydroquinazolines from a
common intermediate and can be extrapolated for similar kinds
of heterocycles for the generation of large libraries in shorter time.
5a
DDQ,
dioxane,
83%
Rearrange-
ment
X
73%
6
O
O
8
7
5
N
N
N
N
N
N
1
2
Scheme 2. Dehydrogenation of 5a and 6a.
Table 2
Dehydrogenation of 6aa
S. no.
Reagent
Conditions
Yieldb (1)
1
2
3
4
5
6
7
8
DDQ
—
—
p-TSA
NBS
Pd–C
S powder
SeO2
Dioxane, reflux, 2 h
Dioxane, reflux, 4 h
Toluene, reflux, 4 h
Toluene, reflux, 4 h
Dioxane, pyridine, reflux, 3 h
Benzene, reflux, 2 h
DMF, reflux, 4 h
70%
No change
No change
No change
35%
35%
70%
Dehydrogenation
quinazolin-8-one with DDQ provided (8H)-quinazolino[4,3-b]qui-
nazolin-8-one. Surprisingly 11b,12-dihydro-(13H)-quinazoli-
of
13,13a-dihydro-(8H)-quinazolino[4,3-b]
no[3,4-a]quinazolin-13-one is rearranged to (8H)-quinazolino
[4,3-b]quinazolin-8-one with the general dehydrogenating
reagents such as DDQ, Pd–C, etc.
AcOH, reflux, 4 h
40%
a
All the reactions were performed with 6a (10 mmol), reagent (15 mmol), and
solvent.
b
Isolated yields.
Acknowledgments
We sincerely thank Sri G. Ganga Raju, Chairman and Mr. G.
Rama Raju, Director, Laila Impex, for support and encouragement.
We are also thankful to Professor A. Srikrishna, the Department of
Organic Chemistry, Indian Institute of Science, Bangalore, India for
helpful discussions.
O
O
N
NH
NH
N
H
N
O
N
6a
References and notes
O
1. (a) Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V. Comprehensive Heterocyclic
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Int. Ed. 2001, 40, 339–346; (c) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem.
Rev. 2003, 103, 893–930.
NH
NH
N
N
N
N
O
N
3. (a) Michael, J. P. Nat. Prod. Rep. 2001, 18, 543–559; (b) Reddy, P. S.; Reddy, P. P.;
Vasantha, T. Heterocycles 2003, 60, 183–226.
NH
N
-H+
4. (a) Connolly, D. J.; Cusack, D.; O’Sullivan, T. P.; Guiry, P. J. Tetrahedron 2005, 61,
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1
Scheme 3. Tentative mechanism of the rearrangement.
5. (a) Hennequin, L. F.; Thomas, A. P.; Johnstone, C.; Stokes, E. S. E.; Ple, P. A.;
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contrary to the expectation, dehydrogenation of 11b,12-dihydro-
(13H)-quinazolino[3,4-a]quinazolin-13-one (6a) with DDQ under
identical conditions, instead of (13H)-quinazolino[3,4-a]quinazo-
lin-13-one (2), gave compound 1 in good yield as shown in Scheme
2. The product is identical in all respects (mp, mixed mp, 1H, and
13C NMR) with 1.
This unusual rearrangement of 6a prompted us to investigate
with other dehydrogenative reagents and the results were summa-
rized in Table 2. First the reaction was carried out without dehy-
drogenation reagent in two solvents and with p-TSA, an acidic
catalyst (entries 2–4). However, there is no reaction confirming
that the rearrangement is not acid catalyzed. With NBS and Pd–
C, only rearranged product 1 was observed (entries 5 and 6).
Refluxing with sulfur powder in DMF or with SeO2 gave again
9. Azizian, J.; Mohammadi, A. A.; Karimi, A. R.; Mohammadizadeh, M. R. J. Chem.
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A. D.; Subramanian, A.; Mukhopadhyay, B.; Roy, R. Tetrahedron Lett. 2006, 47,
6857–6860.
the rearranged product (entries 7 and 8). Perhaps a complete
p-
electron delocalization from carbonyl (C-8) to the adjacent
carbon-6 via two benzene rings made the rearranged product 1

S. Venkateswarlu et al. / Tetrahedron Letters 54 (2013) 128–131
131
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Compound 5c: Off-white color solid (15%), mp 242–244 °C. 1H NMR (400 MHz,
CDCl3): d 8.26 (1H, s), 8.10 (1H, d, J = 8.0 Hz), 7.53 (1H, t, J = 7.8 Hz), 7.11 (1H, t,
J = 7.6 Hz), 7.01 (1H, d, J = 8.4 Hz), 6.91 (1H, s), 6.88 (1H, s), 6.22 (1H, d,
J = 6.0 Hz), 4.58–4.60 (1H, m, exchangeable with D2O), 3.94 (3H, s), 3.91 (3H, s);
13C NMR (100 MHz, CDCl3): d 162.4, 150.4, 148.4, 144.9, 138.5, 135.5, 134.1,
129.9, 122.1, 118.6, 118.5, 112.6, 110.3, 107.5, 64.2, 56.5, 56.1; LC–MS
(negative ion mode): m/z 308 (M–H)–; HRMS-(EI) (m/z) (M+Na)+ Calcd for
12. General procedure for 5 and 6: To a suspension of 4 (1.5 mmol) in toluene
(15 mL) was added successively DMF–DMA (0.4 mL, 3.0 mmol) and
triethylamine (0.2 mL, 1.5 mmol) at rt, stirred for 1 h and refluxed for 3 h.
The reaction mixture was allowed to cool to rt and the precipitated product
was filtered, washed with toluene and dried. The crude product was
recrystallized from chloroform–methanol to give 6. The filtrate from the
reaction mixture was diluted with ice cold water (200 mL) and extracted with
ethyl acetate (3 Â 100 mL). The combined EtOAc layer was washed with brine,
dried over sodium sulfate and filtered. The solution was evaporated and the
residue was chromatographed over silica gel column using chloroform–
methanol (98:2) as eluents to give 5.
C17H15N3O3 332.1011, found 332.1017.
Compound 6c: Off-white color solid (56%), mp 306–308 °C. 1H NMR (400 MHz,
DMSO-d6): d 8.73 (1H, s), 7.98 (1H, d, J = 7.6 Hz), 7.72 (1H, s), 7.62–7.69 (2H,
m), 7.37 (1H, t, J = 7.8 Hz), 6.96 (1H, s), 6.78 (1H, s), 6.43 (1H, s), 3.81 (3H, s),
3.80 (3H, s); 13C NMR (100 MHz, DMSO-d6): d 162.2, 149.7, 146.8, 141.8, 140.9,
133.5, 128.1, 124.9, 122.6, 118.0, 110.3, 109.9, 108.6, 62.2, 55.7, 55.6; LC–MS
(positive ion mode): m/z 310 (M+H)+.
Compound 5d: Off-white color solid (15%), mp 188–190 °C. 1H NMR (400 MHz,
CDCl3): d 8.22 (1H, s), 8.06 (1H, d, J = 2.4 Hz), 7.47 (1H, dd, J = 8.6, 2.2 Hz), 6.97
(1H, d, J = 8.8 Hz), 6.90 (1H, s), 6.86 (1H, s), 6.19 (1H, d, J = 6.4 Hz), 4.60 (1H, d,
J = 6.0 Hz, exchangeable with D2O), 3.93 (3H, s), 3.90 (3H, s); 13C NMR
(100 MHz, CDCl3): d 161.4, 150.5, 148.5, 143.2, 138.1, 135.5, 134.0, 129.2,
127.7, 120.3, 119.8, 112.1, 110.4, 107.5, 64.2, 56.5, 56.1; LC–MS (negative ion
mode): m/z 342, 344 (M–H)–; HRMS-(EI) (m/z) (M+H)+ Calcd for C17H14ClN3O3
344.0802, found 344.0826.
13. Spectroscopic data - Compound 5a: Off-white color solid (22%), mp 226–228 °C.
IR (KBr) mmax 3228, 1687, 1621, 1610, 1308, 1251, 1221, 1171, 1157, 900,
760 cmÀ1 1H NMR (400 MHz, DMSO-d6): d 8.17 (1H, s), 7.85 (1H, d, J = 7.6 Hz),
;
7.64 (1H, d, J = 7.2 Hz), 7.56 (1H, s, exchangeable with D2O), 7.52 (1H, t,
J = 7.6 Hz), 7.42 (1H, t, J = 7.2 Hz), 7.35 (1H, t, J = 7.0 Hz), 7.25 (1H, d, J = 7.2 Hz),
7.10 (1H, d, J = 8.0 Hz), 6.94 (1H, t, J = 7.2 Hz), 6.35 (1H, s); 13C NMR (100 MHz,
DMSO-d6): d 161.8, 147.7, 139.2, 139.1, 135.4, 129.8, 128.7, 126.9, 126.0, 125.8,
121.6, 119.4, 116.6, 114.5, 63.6; LC–MS (positive ion mode): m/z 250 (M+H)+;
HRMS-(EI) (m/z) (M+Na)+ Calcd for C15H11N3O 272.0800, found 272.0804.
Compound 6a: Off-white color solid (51%), mp 296–302 °C. IR (KBr) mmax 3157,
Compound 6d: Off-white color solid (55%), mp 306–308 °C. 1H NMR (400 MHz,
DMSO-d6): d 8.88 (1H, s), 7.91 (1H, s), 7.72 (3H, br s), 6.96 (1H, s), 6.79 (1H, s),
6.43 (1H, s), 3.81 (3H, s), 3.80 (3H, s); LC–MS (positive ion mode): m/z 344, 346
(M+H)+; HRMS-(EI) (m/z) (M+H)+ Calcd for, C17H14ClN3O3 344.0802, found
344.0807.
Compound 5e: Off-white color solid (16%), mp 220–222 °C. 1H NMR (400 MHz,
CDCl3): d 8.22 (1H, s), 8.21 (1H, d, J = 2.0 Hz), 7.60 (1H, dd, J = 8.6, 2.2 Hz), 6.91
(1H, d, J = 7.2 Hz), 6.90 (1H, s), 6.86 (1H, s), 6.19 (1H, d, J = 6.4 Hz), 4.64 (1H, d,
J = 5.6 Hz, exchangeable with D2O), 3.93 (3H, s), 3.90 (3H, s); 13C NMR
(100 MHz, CDCl3): d 161.3, 150.6, 148.6, 143.6, 138.3, 138.1, 134.0, 132.3,
120.4, 120.0, 114.6, 112.1, 110.4, 107.5, 64.1, 56.5, 56.1; LC–MS (negative ion
mode): m/z 386, 388 (M–H)–.
3050, 1686, 1622, 1605, 1314, 1303, 1254, 1182, 760 cmÀ1 1H NMR (400 MHz,
;
DMSO-d6): d 8.76 (1H, s, exchangeable with D2O), 7.98 (1H, d, J = 7.6 Hz), 7.78
(1H, s), 7.69 (1H, t, J = 7.8 Hz), 7.64 (1H, d, J = 7.6 Hz), 7.36–7.41 (3H, m), 7.25
(1H, t, J = 7.4 Hz), 7.20 (1H, d, J = 8.0 Hz), 6.50 (1H, s); 13C NMR (100 MHz,
DMSO-d6): d 162.0, 143.6, 140.8, 139.8, 133.5, 129.9, 128.1, 127.6, 125.8, 125.2,
125.1, 123.1, 118.5, 118.2, 62.0; LC–MS (positive ion mode): m/z 250 (M+H)+;
HRMS-(EI) (m/z) (M+H)+ Calcd for C15H11N3O 250.0980, found 250.0977.
Compound 5b: Off-white color solid (14%), mp 248–250 °C. 1H NMR (400 MHz,
CDCl3): d 8.33 (1H, s), 7.44–7.48 (2H, m), 7.39 (1H, t, J = 7.6 Hz), 7.35 (1H, t,
J = 8.0 Hz), 7.27 (1H, t, J = 7.6 Hz), 6.47 (1H, s), 6.19 (1H, d, J = 7.6 Hz), 4.39 (1H,
d, J = 7.2 Hz, exchangeable with D2O), 3.94 (3H, s), 3.92 (3H, s); 13C NMR
(100 MHz, CDCl3): d 161.9, 156.1, 145.7, 140.6, 140.1, 139.9, 130.4, 127.2,
127.0, 124.8, 121.4, 110.8, 109.9, 101.5, 64.4, 56.3, 56.2; LC–MS (negative ion
mode): m/z 308 (M–H)–.
Compound 6e: Off-white color solid (52%), mp 324–326 °C. 1H NMR (400 MHz,
DMSO-d6): d 8.88 (1H, s, exchangeable with D2O), 8.04 (1H, d, J = 1.2 Hz), 7.85
(1H, dd, J = 8.6, 1.6 Hz), 7.72 (1H, s), 7.65 (1H, d, J = 8.4 Hz), 6.95 (1H, s), 6.79
(1H, s), 6.43 (1H, s), 3.81 (3H, s), 3.80 (3H, s); LC–MS (positive ion mode): m/z
388, 390 (M+H)+; HRMS-(EI) (m/z) (M+H)+ Calcd for, C17H14BrN3O3 388.0297,
found 388.0293.
14. (a) Fu, P. P.; Harvey, R. G. Chem. Rev. 1978, 78, 317–361; (b) Walker, D.; Hiebert,
J. D. Chem. Rev. 1967, 67, 153–195; (c) Trost, B. M. J. Am. Chem. Soc. 1967, 89,
1847–1851; (d) Manley, J. M.; Roper, T. J.; Lash, T. D. J. Org. Chem. 2005, 70,
874–891; (e) Nakamichi, N.; Kawashita, Y.; Hayashi, M. Org. Lett. 2002, 4,
3955–3957; (f) Varma, R. S.; Kumar, D. J. Chem. Soc., Perkin Trans. 1 1999, 1755–
1757; (g) Paquette, L. A.; Ross, R. J.; Springer, J. P. J. Am. Chem. Soc. 1988, 110,
6192–6204; (h) Eynde, J.-J. V.; Mayence, A.; Maquestiau, A. Tetrahedron 1992,
48, 463–468; (i) Shanmugam, P.; Perumal, P. T. Tetrahedron 2006, 62, 9720–
9734; (j) Kotha, S.; Banerjee, S.; Mandal, K. Synlett 2004, 2043–2045.
Compound 6b: Off-white color solid (52%), mp 308–310 °C. 1H NMR (400 MHz,
DMSO-d6): d 8.53 (1H, s, exchangeable with D2O), 7.80 (1H, s), 7.41 (1H, s),
7.35–7.38 (2H, m), 7.18–7.25 (3H, m), 6.42 (1H, s), 3.92 (3H, s), 3.83 (3H, s); 13
C
NMR (100 MHz, DMSO-d6): d 162.0, 153.3, 146.7, 144.0, 139.9, 135.4, 129.8,
127.6, 125.6, 125.1, 118.6, 115.0, 109.5, 102.0, 62.3, 56.2, 55.8; LC–MS (positive
ion mode): m/z 310 (M+H)+; HRMS-(EI) (m/z) (M+H)+ Calcd for C17H15N3O3
310.1192, found 310.1194.