Synthesis of chromeno[2,3-b]indole derivates

Article abstract of DOI:10.3987/COM-13-12780

Several new chromeno[2,3-b]indole tetracycles were synthesized by the reaction of 2'-hydroxyacetophenones or 2'-hydroxypropiophenones and salicylaldehyde derivates. Under the harsh reaction conditions, the initially formed Knoevenagel adducts lost water,

Full text of DOI:10.3987/COM-13-12780

HETEROCYCLES, Vol. 87, No. 10, 2013
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HETEROCYCLES, Vol. 87, No. 10, 2013, pp. 2053 - 2069. © The Japan Institute of Heterocyclic Chemistry
Received, 15th July, 2013, Accepted, 26th August, 2013, Published online, 10th September, 2013
DOI: 10.3987/COM-13-12780
SYNTHESIS OF CHROMENO[2,3-b]INDOLE DERIVATES
Eszter Gráczol-Fördős,a Tibor Novák,a Gábor Blaskó,a Imre Fejes,a
Françoise Perron-Sierra,b and Miklós Nyergesa,*
aServier Research Institute of Medicinal Chemisrty, 7 Záhony utca., H-1031,
Budapest, Hungary
bInstitut de Recherches Servier, 3 rue de la République, 92150 Suresnes, France
Fax: +36(1)8812011; E-mail: miklos.nyerges@hu.netgrs.com
Abstract – Several new chromeno[2,3-b]indole tetracycles were synthesized by
the reaction of 2’-hydroxyacetophenones or 2’-hydroxypropiophenones and
salicylaldehyde derivates. Under the harsh reaction conditions, the initially
formed Knoevenagel adducts lost water, giving rise to the formation of ring
closed tetracyclic products.
During one of our ongoing medicinal chemistry programs we intended to prepare a small library of
1,3-dihydro-[1-(3-hydroxyphenyl)ethylidene]-2H-indol-2-one derivatives 3 using the frequently applied
Knoevenagel reaction between the appropriate 2’-hydroxyacetophenones and oxindole derivatives.1 The
condensation between 2’-hydroxybenzaldehydes and oxindoles is a well-described and often utilized
reaction but to date, there is no example of the use of 2’-hydroxyacetophenones in this process.2
The reactions between oxindole 1 and salicylaldehyde derivatives 2 (R1=OH, R4=H) or other benzaldehyde
derivatives (R1=Br) were performed under the standard conditions for this reaction (EtOH, cat. piperidine,
reflux), giving rise the formation of the expected products in good yields (Table 1, Entries 1-3). Under the
same conditions, the related 2’-hydroxyacetophenones (2, R4 =Me) or propiophenones (2, R4 =Et) did not
react with oxindole 1 and only the starting materials were recovered. After we had investigated several
other harsher sets of reaction conditions we found, that using of n-butylamine as a base, in the presence of
acetic acid in mesitylene at 140 oC, the starting material disappeared accordingly to HPLC. In most cases a
single new product was formed in addition to some decomposition products, arising from the starting
 Dedicated to Professor László Tőke on the occasion of his 80th birthday.

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HETEROCYCLES, Vol. 87, No. 10, 2013
materials. From the mass spectra it was apparent that it was not the expected product 3 which was formed,
and a new tetracycle 4 was isolated as revealed by NMR studies (Scheme 1).
The chromeno[2,3-b]indole ring system has been described only as a by-product in a similar intramolecular
cyclization of o-aminobenzylidene-oxindoles,3 while a few closely related chromono[2,3-b]indoles have
been prepared from the corresponding 3-(2-hydroxybenzoyl)oxindoles4 or, in one case, via an
aminoisoflavone – salicyloylindole ring transformation.5
3'
1
2
3
6
5
4
Scheme 1
The chromeno[2,3-b]indole derivatives (Table 1, Entries 4-26) were formed, in most cases, in fair to good
yields. The nature of the substituent in the aromatic ring of the oxindole 1 or of the acetophenone 2 has little
effect on the yields and the progress of the reaction, although a halogen at position 5 of the acetophenone
decreases the yield of the condensation. In some cases, however, when the crude product was not pure
enough for our purposes (<95%, by HPLC) we could isolate it them after purification (e.g. entries 9 or 26)
only in very low yields due to the sparingly soluble nature of these substances.
We have applied the same reaction conditions to aldehydes (Table 2), however the ring-closed products 4
were formed only in low yields, in addition to the 3 ʻnormalʼ Knoevenagel products in all cases. In the
cyclization of the 5-methyloxindole (R=Me) 1ab with salicylaldehyde (R2=R3=R4=H) 2, a small quantity of
dihydrocoumarin-type product 5ab was also separated. When a stronger base, Hünig’s, base, was utilized
instead of butylamine (Table 2, Entries 2, 5 and 9) the conversions of the reactions increased, but product 3
still remained the major product.

HETEROCYCLES, Vol. 87, No. 10, 2013
2055
Table 1
Entry
R
R1
OH
Br
R2
H
R3
Cl
Cl
R4
H
Methoda 3 (%)b
4% (%)b
3a
(76)
1
2
Br
Br
A
-
-
3b
(53)
H
H
A
3
Ph
H
Br
H
H
H
H
H
H
H
H
H
Br
H
H
H
H
H
H
Br
H
H
H
H
Br
H
H
OH
OMe
OMe
OH
Br
H
A
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
B
3c (60)
-
4
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
Me
Me
Me
Me
Me
Et
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
4d 85 (39)d
4e 79 (15)c
4f 94 (72)c
4g 63 (28)c
4h 86 (45)d
4i 47 (9)e
5
Me
6
Me
7
Me
8
Ph
OMe
Br
9
Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Br
OMe
OH
Cl
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
4j 71 (48)c
4k 73 (64)c
4l 24 (10)c
4m 64 (38)d
4n 80 (79)c
4o 87 (63)c
4p 70 (57)c
4q 84 (29)c
4r 94 (49)c
4s 36 (21)c
4t 55 (21)c
4u 62 (13)d
4v 74 (56)d
4w 96 (74)c
4x 53 (35)d
4y 62 (55)d
4z 27 (5)e
Br
Br
Br
Br
CN
OMe
OH
Br
CN
CN
CF3
CF3
CF3
CF3
CF3
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
OMe
OH
Cl
Br
Br
OMe
OH
Cl
Me
Me
Me
Me
Et
Br
Br
aMethod A: cat. piperidine in ethanol, reflux, 1 h; Method B: 1-butylamine, acetic acid in mesitylene, 140 °C, 24 h
bHPLC yield (isolated yield)method; cafter recrystallization; dafter chromatography ;eafter preparative HPLC.
In these cases other by-products, 5ac and 6, were also identified. Using 2’-hydroxybenzophenone instead of
acetophenones did not result in reaction, only the decomposition of the starting materials was observed
(Table 2, Entry 9).
The formation of the four different isolated products can be explained according to Scheme 2. The initially
formed Knoevenagel adduct 3 loses water under the reaction conditions through its tautomeric form 7,
giving rise to the formation of the ring closed tetracyclic product 4. However, the ring opening of 7
indolenine can lead to carboxylic acid 8, which can undergo immediate intramolecular O-acylation to
product 6, followed by the reaction of the free aniline moiety with an additional molecule of starting
aldehyde to give the byproduct 5.

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HETEROCYCLES, Vol. 87, No. 10, 2013
Table 2
Entry
5 or 6%
(%)b
R
R1
R4 Methoda
3% (%)b
4% (%)b
1
2
H
H
OH
OH
OH
OH
OH
OH
OH
H
H
H
H
H
H
H
H
H
Ph
B
C
B
B
C
B
B
B
C
B
3aa 30 (26)d
3aa 52 (35)d
3ab 45 (40)c 4ab 21 (15)d
3ab 8 (8)d
20
-
4aa 37 (7)d
6aa 2 (2)
5ab 13 (6)d
3
Me
Br
4
4ac 30 (28)d
-
5
Br
39
28
5ac 32 (5)d
6
CN
CF3
3ad 61 (58)d 4ad 20 (16)d
-
-
-
-
-
7
3ae 17 (15)d
3af 37 (26)d
4ae 10 (10)d
8
CO2Me OH
CO2Me OH
2
9
28
4af 13 (3.4)d
10
H
OH
-
-
a
R2 = R3 = H; Method B: 1-butylamine, acetic acid in mesitylene, 140 °C, 2 h; Method C: diisopropylethylamine,
acetic acid in mesitylene; 140 °C, bHPLC yield (isolated yield)method; cafter recrystallization; dafter chromatography;
eafter preparative HPLC.
1
2
3
7
-H2O
4
8
5
6
Scheme 2

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In summary, the reaction described herein represents a simple entry into the synthesis of polyfunctional
chromeno[2,3-b]indole derivatives 4 of potential pharmaceutical interest, for which there have been no
previously described syntheses. Further investigations of the present method will be required to optimize
the yields, and establish its utility and scope.
EXPERIMENTAL
All melting points were obtained on MPA100 Optimelt Automated Melting Point System and are
uncorrected. IR spectra were recorded with a Bruker Tensor 27 FT-IR spectrophotometer. 1H NMR and 13C
spectra were recorded in DMSO-d6 or in pyridine-d5 using TMS as an internal reference on a Bruker
Avance III spectrometer operating at 500 MHz and 125 MHz respectively (1H-, DEPTQ-, HSQC-, HMBC-,
NOE-NMR). High-resolution MS spectra were measured on an Agilent 6230 TOF LC/MS spectrometer.
Elemental analysis was performed on FlashEA 1112 Elemanalyzer.
General Method A: A mixture of 1.0 mmol of oxindole derivate (1), 1.0 mmol of benzaldehyde (2, R4=H),
and 20 µL of piperidine in 3 mL of EtOH was refluxed for 1 h. The precipitated product was collected by
filtration, washed with cold EtOH, and dried in vacuo at 50 °C to give the corresponding product.
General Method B: A mixture of 2.0 mmol of oxindole (1), and 2.0 mmol of 2’-hydroxyacetophenone (2,
R4=Me) or 2’-hydroxypropiophenone (2, R4=Et) or salicilaldehyde (R4=H) derivate was dissolved in 8.0
mL of mesitylene. After stirring for 10 min, 0.30 mL of 1-butylamine (3.0 mmol) and 0.17 mL of acetic
acid (3.0 mmol) were added to the reaction and the mixture was kept at 140 °C for 24 h (in case of the
salicilaldehyde for 2 h). After cooling, the product was precipitated, collected by filtration, washed with
cold EtOAc, and dried in vacuo at 50 °C for overnight. The product obtained was further purified by
recrystallization, column chromatography, or preparative HPLC.
General Method C: A mixture of 1.0 mmol of oxindole and 1.5 mmol of the salicylaldehyde was dissolved
in 4.0 mL of mesitylene. After stirring for 10 min, 0.26 mL of diisopropylethylamine (1.5 mmol) and 0.086
mL of acetic acid (1.5 mmol) were added and the mixture was kept at 140 °C for 2 h. After cooling the
product was precipitated, collected by filtration, washed with iso-propanol and dried in vacuo at 50 °C for
overnight.
5-Bromo-3-[(5-chloro-2-hydroxyphenyl)methylene]indolin-2-one (3a): Compound was synthesized
according to the General Method A. 266.5 mg, (76%); yellow crystals; mp 249 °C. IR (KBr, cm-1): 1694
(>C=O), 1605 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 6.84 (1H, d, J = 8.2 Hz), Ar-H, 7.01 (1H, d, J =
8.8 Hz, Ar-H), 7.38 (1H, dd, J1 = 8.8 Hz, J2 = 2.9 Hz, Ar-H), 7.41 (1H, dd, J1 = 8.2 Hz, J2 = 1.9 Hz, Ar-H),
7.43 (1H, d, J = 1.9 Hz, Ar-H), 7.60 (1H, d, J = 2.9 Hz, Ar-H), 7.61 (1H, s, >C=CH), 10.60 (1H, brs, OH),
10.76 (1H, s, NH). 13C NMR (125 MHz, DMSO-d6): δ = 112.4 (Ar-C), 113.1 (C-Br), 118.3, 122.8 (C-Cl),

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HETEROCYCLES, Vol. 87, No. 10, 2013
123.0, 123.6, 125.4, 127.4 (>C=CH), 129.3, 131.7, 132.7, 132.8 (>C=CH), 142.4, 155.7 (C-OH), 168.5
(NH-C=O). HRMS m/z calcd for C15H10BrClNO2 (M+H)+ 349.9505, found 349.9574. Anal. Calcd for
C15H9BrClNO2: C, 51.39; H, 2.59; N, 4.00%. Found C, 51.47; H, 2.57; N, 3.74%.
5-Bromo-3-[(2-bromo-5-chlorophenyl)methylene]indolin-2-one (3b): Compound was synthesized
according to the General Method A. 219.2 mg (53%); yellow crystals, mp 260 °C. IR (KBr, cm-1): 3180
1
(-NH), 1716 (>C=O), 1612 (C=C). H NMR (500 MHz, DMSO-d6): δ = 6.86 (1H, d, J = 8.3 Hz, Ar-H),
7.05 (1H, d, J = 1.9 Hz, Ar-H), 7.44 (1H, dd, J1 = 8.3 Hz, J2 = 1.9 Hz, Ar-H), 7.51 (1H, s, >C=CH), 7.55 (1H,
dd, J1 = 8.6 Hz, J2 = 2.6 Hz, Ar-H), 7.83 (1H, d, J = 2.6 Hz, Ar-H), 7.86 (1H, d, J = 8.6 Hz, Ar-H), 10.88
13
(1H, brs, NH). C NMR (125 MHz, DMSO-d6): δ = 112.8 (Ar-C), 113.3 (C-Br), 121.8, (C-Br), 122.9,
125.4, 129.7 (>C=CH), 130.2, 131.7, 133.1, 133.6, 134.3 (>C=CH), 135.2, 136.9, (C-Cl), 142.9, 167.9
(NH-C=O). HRMS m/z calcd for C15H9Br2ClNO (M+H)+ 411.8661, found 411.8733. Anal. Calcd for
C15H8Br2ClNO: C, 43.57; H, 1.95; N, 3.39%. Found C, 43.26; H, 1.96; N, 3.16%.
3-[(2-Bromo-5-hydroxyphenyl)methylene]-5-phenylindolin-2-one (3c): Compound was synthesized
according to the General Method A. 235.4 mg, (60%); yellow crystals mp 220 °C. IR (KBr, cm-1): 1694
(>C=O), 1615 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 6.86 (1H, dd, J1 = 8.6 Hz, J2 = 1.9 Hz, Ar-H),
6.97 (1H, d, J = 8.1 Hz, Ar-H), 7.26 (1H, d, J = 1.9 Hz, Ar-H), 7.29-7.43 (5H, m, Ar-H), 7.51 (1H, s,
>C=CH), 7.52 (1H, s, Ar-H), 7.55 (1H, d, J = 8.1 Hz, Ar-H), 7.58 (1H, d, J = 8.6 Hz, Ar-H), 10.07 (1H, s,
OH), 10.79 (1H, s, NH). 13C NMR (125 MHz, DMSO-d6): δ = 111.1 (Ar-C), 112.0 (C-Br), 117.2, 119.3,
121.6, 121.6, 126.5, 127.5, 129.4, 129.4 (>C=CH), 129.7, 133.9 (C-Ph), 134.3, 134.8 (>C=CH), 135.6,
140.5, 143.1, 157.4 (C-OH), 168.7 (NH-C=O). HRMS m/z calcd for C21H15NO2Br (M+H)+ 392.0208,
found 392.0274. Anal. Calcd for C21H14NO2Br: C, 64.30; H, 3.60; N, 3.57%. Found C, 63.56; H, 3.57; N,
3.28%.
3-(2-Hydroxybenzylidene)-1,3-dihydroindol-2-one (3aa): Compound was synthesized according to the
General Method B. 123.4 mg (26%); yellow crystals; mp 100 °C. IR (KBr, cm-1): 3177 (NH or OH), 1677
(>C=O), 1603 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 6.85 (1H, t, J = 7.7 Hz, Ar-H), 6.86 (1H, d, J =
7.7 Hz, Ar-H, 6.92 (1H, t, J = 7.5 Hz, Ar-H), 6.98 (1H, d, J = 8.0 Hz, Ar-H), 7.21 (1H, t, J = 7.7 Hz, Ar-H),
7.31 (1H, dd, J1 = 8.0 Hz, J2 = 7.5 Hz, Ar-H), 7.50 (1H, d, J = 7.7 Hz, Ar-H), 7.63 (1H, d, J = 7.5 Hz, Ar-H),
7.68 (1H, s, >C=CH), 10.18 (1H, s, OH), 11.12 (1H, s, NH). 13C NMR (125 MHz, DMSO-d6): δ = 110.4
(Ar-C), 116.4, 119.3, 121.5, 121.7, 121.8, 122.8, 126.9 (>C=CH), 130.0, 130.2, 132.1, 132.9 (>C=CH),
143.1, 157.0 (C-OH), 169.2 (NH-C=O). HRMS m/z calcd for C15H12NO2 (M+H)+ 238.0790, found
238.0866. Anal. calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90%. Found C, 75.13; H, 4.86; N, 5.64%.
3-[(2-Hydroxyphenyl)methylene]-5-methylindolin-2-one (3ab): Compound was synthesized according
to the General Method B. 201 mg (40%); yellow crystals, mp 173 °C. IR (KBr, cm-1): 3187 (NH or OH),
1679 (>C=O). 1H NMR (500 MHz, DMSO-d6): δ = 2.15 (3H, s, CH3), 6.75 (1H, d, J = 8.0 Hz, Ar-H), 6.93

HETEROCYCLES, Vol. 87, No. 10, 2013
2059
(1H, t, J = 8.0 Hz, Ar-H), 6.97 (1H, dd, J1 = 8.0 Hz, J2 = 1.0 Hz, Ar-H), 7.02 (1H, bd, J = 8.0 Hz, Ar-H),
7.31 (1H, td, J1 = 7.5 Hz, J2 = 2.0 Hz, Ar-H), 7.33 (1H, d, J = 1.0 Hz, Ar-H), 7.63 (1H, dd, J1 = 7.5 Hz, J2 =
1.5 Hz, Ar-H), 7.65 (1H, s, =C-H), 10.16 (1H, br OH), 10.44 (1H, s, NH). 13C NMR (125 MHz, DMSO-d6):
δ = 21.3 (CH3) , 110.1, 116.4, 119.2, 121.8, 121.8, 123.3, 127.0 (>C=CH), 130.0, 130.0, 130.6, 132.1, 132.7
(>C=CH), 140.8, 157.0 (C-OH), 169.3 (NH-C=O). HRMS calcd for C16H14NO2 (M+H)+ 252.1024, found
252.1020. Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57%. Found C, 76.00; H, 5.15; N, 5.33%.
5-Bromo-3-[(2-hydroxyphenyl)methylene]indolin-2-one (3ac): Compound was synthesized according
to the General Method B. 50.5 mg (8%); yellow crystals, mp 203 °C. IR (KBr, cm-1): 3172 (NH or OH),
1685, 1605 (>C=O). 1H NMR (500 MHz, DMSO-d6): δ = 6.83 (1H, d, J = 8.0 Hz, Ar-H), 6.95 (1H, t, J = 7.8
Hz, Ar-H), 7.00 (1H, d, J = 8.5 Hz, Ar-H), 7.35 (1H, t, J = 7.3 Hz, Ar-H), 7.39 (1H, d, J = 8.0 Hz, Ar-H),
7.52 (1H, bs, Ar-H), 7.58 (1H, d, J = 7.5 Hz, Ar-H), 7.73 (1H, s, =C-H), 10.29 (1H, br OH), 10.72 (1H, s,
NH). 13C NMR (125 MHz, DMSO-d6): δ = 112.3, 113.0, 116.6, 119.3, 121.3, 123.9, 125.1, 126.1 (>C=CH),
130.1, 132.4, 132.6, 134.8 (>C=CH), 142.2, 157.1 (C-OH), 168.8 (NH-C=O). HRMS m/z calcd for
C15H11BrNO2 (M+H)+ 315.9973, found 315.9970. Anal. Calcd for C15H10BrNO2: C, 56.99; H, 3.19; N,
4.43%. Found C, 56.56; H, 3.15; N, 3.99%.
3-[(2-Hydroxyphenyl)methylene]-2-oxoindoline-5-carbonitrile (3ad): Compound was synthesized
according to the General Method B. 304.2 mg (58%); yellow crystals, mp 243 °C. IR (KBr, cm-1): 3278
(NH or OH), 2231 (nitrile), 1715 (>C=O), 1603 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 6.98 (1H, t, J
= 7.6 Hz, Ar-H), 7.02 (1H, d, J = 7.6 Hz, Ar-H), 7.02 (1H, d, J = 6.9 Hz, Ar-H), 7.38 (1H, t, J = 7.6 Hz,
Ar-H), 7.63 (1H, d, J = 7.6 Hz, Ar-H), 7.68 (1H, s, Ar-H), 7.69 (1H, d, J = 6.9 Hz, Ar-H), 7.83 (1H, s,
13
>C=CH), 10.37 (1H, brs, OH), 11.12 (1H, s, NH). C NMR (125 MHz, DMSO-d6): δ = 103.5 (C-CN),
111.2 (Ar-C), 116.7, 119.6, 119.9 (C-CN), 121.2, 122.5, 125.0, 126.0, 130.3, 132.9, 134.6, 135.9, 146.7,
157.2, 169.0. HRMS m/z calcd for C16H11N2O2 (M+H)+ 263.0742, found 263.0820. Anal. Calcd for
C16H10N2O2: C, 73.27; H, 3.84; N, 10.68%. Found C, 72.30; H, 3.45; N, 10.43%.
3-[(2-Hydroxyphenyl)methylene]-5-(trifluoromethyl)indolin-2-one (3ae): Compound was synthesized
according to the General Method B. 91.6 mg (15%); yellow crystals, mp 202 °C. IR (KBr, cm-1): 3176 (NH
or OH), 1691, 1605 (>C=O), 1329, 1104 (CF3). 1H NMR (500 MHz, DMSO-d6): δ = 6.94 (1H, t, J = 7.5 Hz,
Ar-H), 7.01 (1H, dm, J = 8.0 Hz, Ar-H), 7.05 (1H, d, J = 8.0 Hz, Ar-H), 7.36 (1H, t, J = 7.6 Hz, Ar-H), 7.58
(1H, d, J = 8.5 Hz, Ar-H), 7.61 (1H, dm, J = 7.5 Hz, Ar-H), 7.69 (1H, bs, Ar-H), 7.80 (1H, s, =C-H), 10.33
(1H, s OH), 10.99 (1H, s, NH). 13C NMR (125 MHz, DMSO-d6): δ = 110.7, 116.7, 119.1, 119.3, 121.2,
121.9, 122.1, 125.1 (CF3), 125.8 (>C=CH), 127.3, 130.1, 132.8, 135.3 (>C=CH), 146.2, 157.1 (C-OH),
169.1 (NH-C=O). HRMS m/z calcd for C16H11F3NO2 (M+H)+ 300.0741, found 306.0738. Anal. Calcd for
C16H10F3NO2: C, 62.96; H, 3.30; N, 4.59%. Found C, 62.96; H, 2.26; N, 4.05%.

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HETEROCYCLES, Vol. 87, No. 10, 2013
Methyl 3-[(2-hydroxyphenyl)methylene]-2-oxoindoline-5-carboxylate (3af): Compound was
synthesized according to the General Method B. 153.6 mg (26%); yellow crystals, mp 205 °C. IR (KBr,
cm-1): 1704 (>C=O), 1607 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 3.76 (3H, s, OCH3), 6.94 (1H, t, J =
7.6 Hz, Ar-H), 6.97 (1H, d, J = 7.7 Hz, Ar-H), 7.01 (1H, d, J = 7.6 Hz, Ar-H), 7.36 (1H, t, J = 7.6 Hz, Ar-H),
7.64 (1H, d, J = 7.6 Hz, Ar-H), 7.78 (1H, s, >C=CH), 7.86 (1H, dd, J1 = 7.7 Hz, J2 = 1.2 Hz, Ar-H), 8.16 (1H,
brs, Ar-H), 10.27 (1H, s, OH), 10.97 (1H, s, NH). 13C NMR (125 MHz, DMSO-d6): δ = 52.2 (OCH3), 110.2
(Ar-C), 116.6, 119.3, 121.4, 121.9, 122.7 (CCO2Me), 123.8, 125.9 (C=CH), 130.1, 131.8, 132.6, 134.5
(C=CH), 147.1, 157.2 (C-OH), 166.5 (COOMe), 169.5 (NH-C=O). HRMS m/z calcd for C17H14NO4
(M+H)+ 296.0845, found 296.0918. Anal. Calcd for C17H13NO4: C, 69.15; H, 4.44; N, 4.74%. Found C,
68.40; H, 4.28; N, 4.66%.
2-Methoxy-11-methylchromeno[2,3-b]indole (4d): Compound was synthesized according to the General
Method B. 205.3 mg (39%), orange crystals, mp 166 °C. IR (KBr, cm-1): 2922 (C-H), 1192 (C-O-C). 1H
NMR (500 MHz, DMSO-d6): δ = 3.02 (3H, s, CH3), 3.92 (3H, s, OCH3), 7.28 (1H, m, C3-H), 7.40 (1H, dd,
J1 = 9.1 Hz, J2 = 2.9 Hz, C8-H), 7.48 (1H, m, C2-H), 7.55 (1H, d, J = 9.1 Hz, C1-H), 7.58 (1H, d, J = 2.9 Hz,
C6-H), 7.75 (1H, d, J = 9.1 Hz, C9-H), 8.16 (1H, d, J = 7.6 Hz, C4-H). 13C NMR (125 MHz, DMSO-d6): δ =
15.6 (CH3), 56.4 (OCH3), 109.0 (C6), 118.9 (C9), 119.0 (C1), 120.0 (C8), 121.3 (C5a), 122.2 (C4b), 122.4 (C3),
124.0 (C4), 124.4 (C4a), 129.3 (C2), 144.4 (CCH3), 145.5 (C9a), 152.6 (C11a), 156.2 (COCH3), 163.7 (C10a).
HRMS m/z calcd for C17H14NO2 (M+H)+ 264.0946, found 264.1009. Anal. Calcd for C17H13NO2: C, 77.55;
H, 4.98; N, 5.32%. Found C, 76.46; H, 5.15; N, 4.96%.
2-Methoxy-9,11-dimethylchromeno[2,3-b]indole (4e): Compound was synthesized according to the
General Method B. 83.2 mg, (15%); orange crystals; mp 189 °C. IR (KBr, cm-1): 2916 (C-H), 1644 (C=N),
1201 (C-O-C). 1H NMR (500 MHz, pyridine-d5): δ = 2.51 (3H, s, C3-CH3), 2.87 (3H, s, C5-CH3), 3.86 (3H,
s, OCH3), 7.30 (1H, dd, J1 = 9.0 Hz, J2 = 2.9 Hz, C8-H), 7.41 (1H, d, J = 7.9 Hz, C2-H), 7.45 (1H, d, J = 2.9
Hz, C6-H), 7.58 (1H, d, J = 9.0 Hz, C9-H), 7.85 (1H, d, J = 7.9 Hz, C1-H), 7.95 (1H, brs, C4-H). 13C NMR
(125 MHz, pyridine-d5): δ = 14.6 (C5-CH3), 21.2 (C3-CH3), 55.7 (OCH3), 108.6 (C6), 118.4 (C9), 118.8 (C8),
119.0 (C1), 121.4 (C5a), 123.4 (C4b), 124.0 (C4), 125.0 (C4a), 130.0 (C2), 131.3 (C3-CH3), 142.0 (C5-CH3),
145.8 (C9a), 151.6 (C11a), 156.2 (COCH3), 163.7 (C=N, C10a). HRMS m/z calcd for C18H16NO2 (M+H)+
278.1103, found 278.1178. Anal. calcd for C18H15NO2: C, 77.96; H, 5.45; N, 5.05%. Found C, 77.66; H,
5.36; N, 4.91%.
9,11-Dimethylchromeno[2,3-b]indol-2-ol (4f): Compound was synthesized according to the General
Method B. 379.2 mg (72%); mp 278 °C. IR (KBr, cm-1): 1644 (C=N), 1549 (aromatic). 1H NMR (500 MHz,
pyridine-d5): δ = 2.50 (3H, s, C3-CH3), 2.82 (3H, s, C5-CH3), 7.39 (1H, brd, J = 7.9 Hz, C2-H), 7.44 (1H, dd,
J1 = 8.9 Hz, J2 = 2.7 Hz, C8-H), 7.58 (1H, d, J = 8.9 Hz, C9-H), 7.63 (1H, d, J = 2.7 Hz, C6-H), 7.85 (1H, d,
J = 7.9 Hz, C1-H), 7.94 (1H, brs, C4-H), 11.76 (1H, vbrs, OH). 13C NMR (125 MHz, pyridine-d5): δ = 14.5

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(C5-CH3), 21.3 (C3-CH3), 110.7 (C6), 118.3 (C9), 118.9 (C1), 120.3 (C8), 121.7 (C5a), 123.1 (C4b), 124.0 (C4),
125.0 (C4a), 129.9 (C2), 131.1 (C3-CH3), 142.2 (C5-CH3), 145.0 (C9a), 151.6 (C11a), 155.1 (C7-OH), 163.9
(C=N, C10a). HRMS m/z calcd for C17H14NO2 (M+H)+ 264.0946, found 264.1022. Anal. Calcd for
C17H13NO2: C, 77.55; H, 4.98; N, 5.32%. Found C, 76.90; H, 4.86; N, 5.12%.
2-Bromo-9,11-dimethylchromeno[2,3-b]indole (4g): Compound was synthesized according to the
General Method B. 224.5 mg (28%); orange crystals, mp 243 °C. IR (KBr, cm-1): 1649 (C=N), 1552
(aromatic). 1H NMR (500 MHz, pyridine-d5): δ = 2.51 (3H, s, C3-CH3), 2.82 (3H, s, C5-CH3), 7.41 (1H, brd,
J = 7.9 Hz, C2-H), 7.49 (1H, d, J = 8.8 Hz, C9-H), 7.75 (1H, dd, J1 = 8.8 Hz, J2 = 2.1 Hz, C8-H), 7.83 (1H, d,
J = 7.9 Hz, C1-H), 7.93 (1H, brs, C4-H), 8.13 (1H, d, J = 2.1 Hz, C6-H). 13C NMR (125 MHz, pyridine-d5):
δ = 14.5 (C5-CH3), 21.2 (C3-CH3), 116.7 (C7-Br), 119.2 (C1), 119.3 (C9), 122.6 (C5a), 124.0 (C4b), 124.3
(C4), 124.9 (C4a), 128.1 (C6), 130.4 (C2), 131.9 (C3-CH3), 133.9 (C8), 140.7 (C5-CH3), 150.2 (C9a), 151.4
(C11a), 163.1 (C=N, C10a). HRMS m/z calcd for C17H13BrNO (M+H)+ 326.0102, found 326.0183. Anal.
Calcd for C17H12BrNO: C, 62.60; H, 3.71; N, 4.29%. Found C, 61.63; H, 3.58; N, 4.04%.
2-Methoxy-11-methyl-9-phenylchromeno[2,3-b]indole (4h): Compound was synthesized according to
the General Method B. 305.5 mg, (45%); mp 174 °C. IR (KBr, cm-1): 1641 (C=N), 1208 (C-O-C); 1H NMR
(500 MHz, DMSO-d6): δ = 3.10 (3H, s, CH3), 3.93 (3H, s, OCH3), 7.39-7.35 (1H, m, p-Ar-H), 7.41 (1H, dd,
J1 = 9.1 Hz, J2 = 2.9 Hz, C8-H), 7.52-7.47 (2H, m, m-Ar-H), 7.61 (1H, d, J = 2.9 Hz, C6-H), 7.63 (1H, d, J =
8.2 Hz, C1-H), 7.77 (1H, dd, J1 = 9.0 Hz, J2 = 3.8 Hz, C2-H), 7.79 (1H, d, J = 2.9 Hz, C9-H), 7.80-7.78 (2H,
m, o-Ar-H), 8.35 (1H, d, J = 1.7 Hz, C4-H). 13C NMR (125 MHz, DMSO-d6): δ = 15.8 (CH3), 56.4 (OCH3),
108.9 (C6), 119.0 (C9), 119.3 (C1), 120.3 (C8), 121.3 (C5a), 122.3 (C4), 122.3 (C4b), 125.1 (C4a), 127.3
(p-Ar-C), 127.4 (o-Ar-C), 128.1 (C2), 129.4 (m-Ar-C), 134.8 (C3), 141.2 (C3-C), 145.1 (CCH3), 145.6 (C9a),
152.1 (C11a), 156.3 (COCH3), 164.0 (C10a). HRMS m/z calcd for C23H18NO2 (M+H)+ 340.1259, found =
340.1325. Anal. Calcd for C23H17NO2: C, 81.04; H, 5.05; N, 4.13%. Found C, 81.44; H, 5.22; N, 4.14%.
2-Bromo-11-ethyl-9-phenylchromeno[2,3-b]indole (4i): Compound was synthesized according to the
General Method B. 72.4 mg (9%); orange crystals, mp 218 °C. IR (KBr, cm-1): 1638 (C=N), 1547 (C=C).
1H NMR (500 MHz, DMSO-d6): δ = 1.41 (3H, t, J = 7.6 Hz, CH2CH3), 3.57 (2H, q, J = 7.6 Hz, CH2CH3),
7.38 (1H, t, J = 7.4 Hz, p-Ar-H), 7.51 (1H, t, J = 7.4 Hz, m-Ar-H), 7.67 (1H, d, J = 8.2 Hz, C1-H), 7.78 (1H,
d, J = 7.4 Hz, o-Ar-H), 7.81 (1H, dd, J1 = 8.2 Hz, J2 = 1.6 Hz, C2-H), 7.82 (1H, d, J = 8.8 Hz, C9-H), 7.97
(1H, dd, J1 = 8.8 Hz, J2 = 2.2 Hz, C8-H), 8.26 (1H, d, J = 1.6 Hz, C4-H), 8.42 (1H, d, J = 2.2 Hz, C6-H). 13C
NMR (125 MHz, DMSO-d6): δ = 13.7 (CH2CH3), 21.8 (CH2CH3), 117.4 (C7-Br), 119.7 (C1), 120.5 (C9),
121.5 (C5a), 122.1 (C4), 122.3 (C4b), 124.5 (C4a), 127.5 (p-Ar-C), 127.5 (o-Ar-C), 128.4 (C6), 128.6 (C2),
129.5 (m-Ar-C), 135.1 (C8), 135.5 (C3), 141.1 (C3-C), 149.3 (CCH2CH3), 150.6 (C9a), 152.1 (C11a), 163.9
(C10a). HRMS m/z calcd for C23H17BrNO (M+H)+ 402.0415, found 402.0498. Anal. Calcd for C23H16BrNO:
C, 68.67; H, 4.01; N, 3.48%. Found C, 67.79; H, 4.03; N, 3.22%.

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9-Bromo-2-methoxy-11-methylchromeno[2,3-b]indole (4j): Compound was synthesized according to
the General Method B. 328.5 mg, (48%); orange crystals, mp 202 °C. IR (KBr, cm-1): 1642 (C=C), 1537
(aromatic), 1232 (C-O-C). 1H NMR (500 MHz, DMSO-d6): δ = 3.05 (3H, s, CH3), 3.93 (3H, s, OCH3), 7.44
(1H, dd, J1 = 9.1 Hz, J2 = 2.9 Hz, C8-H), 7.51 (1H, d, J = 8.4 Hz, C1-H), 7.62 (1H, d, J = 2.9 Hz, C6-H), 7.64
(1H, d, J = 8.4 Hz, C2-H), 7.78 (1H, d, J = 9.1 Hz, C9-H), 8.31 (1H, brs, C4-H) ppm. 13C NMR (125 MHz,
DMSO-d6): δ = 15.9 (C5-CH3), 56.4 (OCH3), 109.0 (C6), 114.4 (C3-Br), 119.1 (C9), 120.8 (C1), 120.9 (C8),
121.2 (C4b), 121.3 (C5a), 126.3 (C4), 126.3 (C4a), 131.7 (C2), 145.8 (C9a), 146.8 (C5-CH3), 151.5 (C11a),
156.4 (COCH3), 163.8 (C=N, C10a). HRMS m/z calcd for C17H13BrNO2 (M+H)+ 342.0051, found 342.0126.
Anal. Calcd for C17H12BrNO2: C, 59.67; H, 3.53; N, 4.09%. Found C, 58.86; H, 3.38; N, 3.84%.
9-Bromo-11-methylchromeno[2,3-b]indol-2-ol (4k): Compound was synthesized according to the
General Method B. 420.1 mg (64%); orange crystals, mp 302 °C. IR (KBr, cm-1): 1547 (aromatic), 1061
1
(Ar-Br). H NMR (500 MHz, DMSO-d6): δ = 2.95 (3H, s, CH3), 7.26 (1H, dd, J1 = 8.9 Hz, J2 = 2.8 Hz,
C8-H), 7.44 (1H, d, J = 2.8 Hz, C6-H), 7.49 (1H, d, J = 8.4 Hz, C1-H), 7.61 (1H, dd, J1 = 8.4 Hz, J2 = 1.9 Hz,
C2-H), 7.66 (1H, d, J = 8.9 Hz, C9-H), 8.25 (1H, d, J = 1.9 Hz, C4-H), 9.98 (1H, s, OH). 13C NMR (125 MHz,
DMSO-d6): δ = 15.7 (C5-CH3), 110.6 (C6), 114.3 (C3), 118.9 (C9), 120.7 (C1), 121.1 (C4b), 121.3 (C5a),
121.4 (C8), 126.1 (C4), 126.3 (C4a), 131.5 (C2), 144.7 (C9a), 146.6 (C5-CH3), 151.5 (C11a), 154.6 (C7-OH),
163.9 (C=N, C10a). HRMS m/z calcd for C16H11BrNO2 (M+H)+ 327.9895, found 327.9970. Anal. Calcd for
C16H10BrNO2: C, 58.56; H, 3.07; N, 4.27%. Found C, 58.48; H, 2.98; N, 3.96%.
4,9-Dibromo-2-chloro-11-methylchromeno[2,3-b]indole (4l): Compound was synthesized according to
the General Method B. 85.1 mg, (10%); red crystal, mp 284 °C. IR (KBr, cm-1): 1639 (aromatic), 1063
(Ar-Br). 1H NMR (500 MHz, DMSO-d6): δ = 3.03 (3H, s, CH3), 7.56 (1H, d, J = 8.4 Hz, C1-H), 7.70 (1H,
dd, J1 = 8.4 Hz, J2 = 2.0 Hz, C2-H), 8.30 (1H, d, J = 2.3 Hz, C8-H), 8.33 (1H, d, J = 2.3 Hz, C6-H), 8.36 (1H,
13
d, J = 2.0 Hz, C4-H). C NMR (125 MHz, DMSO-d6): δ = 16.0 (C5-CH3), 112.3 (C9-Br), 115.3 (C3-Br),
121.3 (C1), 121.5 (C5a), 122.0 (C4b), 126.1 (C6), 126.3 (C4a), 126.7 (C4), 129.5 (C7-Cl), 132.5 (C2), 135.0
(C8), 145.4 (C5-CH3), 146.7 (C9a), 151.2 (C11a), 164.7 (C=N, C10a). HRMS m/z calcd for C16H9Br2ClNO
(M+H)+ 423.8661, found 425.8722. Anal. Calcd for C16H8Br2ClNO: C, 45.16; H, 1.89; N, 3.29%. Found C,
45.12; H, 1.87; N, 3.10%.
2,9-Dibromo-11-methylchromeno[2,3-b]indole (4m): Compound was synthesized according to the
General Method B. 297.2 mg (38%); orange crystals, mp 234 °C. IR (KBr, cm-1): 1544 (aromatic), 1077
(Ar-Br). 1H NMR (500 MHz, DMSO-d6): δ = 3.05 (3H, s, CH3), 7.56 (1H, d, J = 8.4 Hz, C1-H), 7.68 (1H,
dd, J1 = 8.4 Hz, J2 = 1.9 Hz, C2-H), 7.82 (1H, d, J = 8.9 Hz, C9-H), 8.00 (1H, dd, J1 = 8.9 Hz, J2 = 2.3 Hz,
C8-H), 8.34 (1H, d, J = 1.9 Hz, C4-H), 8.42 (1H, d, J = 2.3 Hz, C6-H). 13C NMR (125 MHz, DMSO-d6): δ =
15.8 (C5-CH3), 115.0 (C3), 117.3 (C7), 120.3 (C9), 121.1 (C1), 122.1 (C4b), 122.6 (C5a), 126.4 (C4a), 126.5
(C4), 129.2 (C6), 132.1 (C2), 135.4 (C8), 145.8 (C5-CH3), 150.3 (C9a), 151.4 (C11a), 163.5 (C=N, C10a).

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HRMS m/z calcd for C16H10Br2NO (M+H)+ 389.9051, found 391.9104. Anal. Calcd for C16H9Br2NO: C,
49.14; H, 2.32; N, 3.58%. Found C, 48.76; H, 2.26; N, 3.37%.
2-Methoxy-11-methylchromeno[2,3-b]indole-9-carbonitrile (4n): Compound was synthesized
according to the General Method B. 455.5 mg, (79%); yellow crystals, mp 259 °C. IR (KBr, cm-1): 2215
(nitrile), 1644 (C=N), 1233 (C-O-C). 1H NMR (500 MHz, pyridine-d5): δ = 2.95 (3H, s, C5-CH3), 3.90 (3H,
s, OCH3), 7.42 (1H, dd, J1 = 9.1 Hz, J2 = 2.9 Hz, C8-H), 7.55 (1H, d, J = 2.9 Hz, C6-H), 7.66 (1H, d, J = 9.1
Hz, C9-H), 7.88 (1H, dd, J1 = 8.2 Hz, J2 = 1.2 Hz, C2-H), 7.90 (1H, d, J = 8.2 Hz, C1-H), 8.50 (1H, brs,
13
C4-H). C NMR (125 MHz, pyridine-d5): δ = 15.0 (C5-CH3), 55.8 (OCH3), 104.8 (C3-CN), 108.6 (C6),
118.8 (C9), 119.8 (C1), 120.3 (C3-CN), 120.5 (C8), 121.2 (C5a), 121.5 (C4b), 125.0 (C4a), 127.3 (C4), 132.5
(C2), 146.0 (C9a), 146.4 (C5-CH3), 156.5 (C11a), 156.7 (COCH3), 163.9 (C=N, C10a). HRMS m/z calcd for
C18H13N2O2 (M+H)+ 289.0898, found 289.0973. Anal. Calcd for C18H12N2O2: C, 74.99; H, 4.20; N, 9.72%.
Found C, 74.62; H, 4.10; N, 9.59%.
2-Hydroxy-11-methylchromeno[2,3-b]indole-9-carbonitrile (4o): Compound was synthesized
according to the General Method B. 345.6 mg, (63%); brown crystals, mp 319 °C. IR (KBr, cm-1): 2216
(nitrile), 1643 (C=N), 1527 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 3.05 (3H, s, C5-CH3), 7.33 (1H, dd,
J1 = 9.0 Hz, J2 = 2.8 Hz, C8-H), 7.51 (1H, d, J = 2.8 Hz, C6-H), 7.70 (1H, d, J = 8.2 Hz, C1-H), 7.75 (1H, d,
J = 9.0 Hz, C9-H), 7.90 (1H, dd, J1 = 8.2 Hz, J2 = 1.5 Hz, C2-H), 8.68 (1H, d, J = 1.5 Hz, C4-H), 10.11 (1H,
13
brs, OH). C NMR (125 MHz, DMSO-d6): δ = 15.9 (C5-CH3), 104.0 (C3-CN), 110.7 (C6), 119.2 (C9),
119.7 (C1), 120.4 (C3-CN), 120.5 (C4b), 121.4 (C5a), 122.0 (C8), 124.9 (C4a), 127.9 (C4), 132.8 (C2), 144.9
(C9a), 148.4 (C5-CH3), 154.9 (C7-OH), 155.8 (C11a), 163.9 (C=N, C10a). HRMS m/z calcd for C17H11N2O2
(M+H)+ 275.0742, found 275.0822. Anal. Calcd for C17H10N2O2: C, 74.45; H, 3.67; N, 10.21%. Found C,
70.64; H, 3.45; N, 9.51%.
2-Bromo-11-methylchromeno[2,3-b]indole-9-carbonitrile (4p): Compound was synthesized according
to the General Method B. 384.4 mg (57%); yellow crystals, mp 247 °C. IR (KBr, cm-1): 2216 (nitrile), 1642
(C=N). 1H NMR (500 MHz, pyridine-d5): δ= 2.91 (3H, s, C5-CH3), 7.59 (1H, d, J = 8.8 Hz, C9-H), 7.87 (1H,
dd, J1 = 8.8 Hz, J2 = 2.3 Hz, C8-H), 7.88-7.90 (1H, m, C1-H), 7.88-7.90 (1H, m, C2-H), 8.28 (1H, d, J = 2.3
Hz, C6-H), 8.49 (1H, s, C4-H). 13C NMR (125 MHz, pyridine-d5): δ =14.9 (C5-CH3), 105.4 (C3-CN), 117.6
(C7-Br), 119.7 (C9), 120.0 (C3-CN), 120.1 (C1), 122.2 (C4b), 122.3 (C5a), 125.0 (C4a), 127.5 (C4), 128.6 (C6),
133.0 (C2), 135.2 (C8), 145.2 (C5-CH3), 150.3 (C9a), 156.4 (C11a), 165.4 (C=N, C10a). HRMS m/z calcd for
C17H10BrN2O (M+H)+ 336.9898, found 336.9981. Anal. Calcd for C17H9BrN2O: C, 60.56; H, 2.69; N,
8.31%. Found C, 60.96; H, 2.72; N, 8.59%.
2-Methoxy-11-methyl-9-(trifluoromethyl)chromeno[2,3-b]indole (4q): Compound was synthesized
according to the General Method B. 192.2 mg, (29%); brown crystals, mp 223 °C. IR (KBr, cm-1): 1541
1
(aromatic), 1331, 1154 (CF3). H NMR (500 MHz, pyridine-d5): δ = 2.97 (3H, s, C5-CH3), 3.88 (3H, s,

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OCH3), 7.39 (1H, dd, J1 = 9.0 Hz, J2 = 2.9 Hz, C8-H), 7.54 (1H, d, J = 2.9 Hz, C6-H), 7.65 (1H, d, J = 9.0 Hz,
C9-H), 7.91 (1H, dd, J1 = 8.2 Hz, J2 = 1.2 Hz, C2-H), 7.99 (1H, d, J = 8.2 Hz, C1-H), 8.46 (1H, brs, C4-H).
13C NMR (125 MHz, pyridine-d5): δ = 14.9 (C5-CH3), 55.8 (OCH3), 108.7 (C6), 118.7 (C9), 119.4 (C1),
120.1 (C8), 120.3 (C4), 121.2 (C5a), 122.1 (C4b), 123.4 (C3-CF3), 124.7 (C4a), 125.6 (C3-CF3), 125.8 (C2),
145.6 (C5-CH3), 146.0 (C9a), 156.2 (C11a), 156.6 (COCH3), 165.5 (C=N, C10a). HRMS m/z calcd for
C18H13F3NO2 (M+H)+ 332.0820, found 332.0881. Anal. Calcd for C18H12F3NO2: C, 65.26; H, 3.65; N,
4.23%. Found C, 65.20; H, 3.56; N, 3.98%;
11-Methyl-9-(trifluoromethyl)chromeno[2,3-b]indol-2-ol (4r): Compound was synthesized according to
the General Method B. 310.9 mg (49%); yellow crystals, mp 302 °C. IR (KBr, cm-1): 1549 (aromatic), 1329,
1105 (CF3). 1H NMR (500 MHz, pyridine-d5): δ = 2.88 (3H, s, CH3), 7.52 (1H, dd, J1 = 8.9 Hz, J2 = 2.8 Hz,
C8-H), 7.64 (1H, d, J = 8.9 Hz, C9-H), 7.70 (1H, d, J = 2.8 Hz, C6-H), 7.90 (1H, dd, J1 = 8.3 Hz, J2 = 1.1 Hz,
13
C2-H), 7.98 (1H, d, J = 8.3 Hz, C1-H), 8.43 (1H, brs, C4-H), 11.97 (1H, brs, OH). C NMR (125 MHz,
pyridine-d5): δ = 14.8 (C5-CH3), 110.8 (C6), 118.6 (C9), 119.3 (C1), 120.2 (C4), 121.5 (C8), 121.5 (C5a),
121.8 (C4b), 123.1 (C3), 124.8 (C4a), 125.7 (C2), 125.7 (C3-CF3), 145.1 (C9a), 145.7 (C5-CH3), 155.5
(C7-OH), 156.2 (C11a), 165.7 (C=N, C10a). HRMS m/z calcd for C17H11F3NO2 (M+H)+ 318.0664, found
318.0726. Anal. Calcd for C17H10F3NO2: C, 64.36; H, 3.18; N, 4.41%. Found C, 63.89; H, 3.27; N, 4.16%.
4-Bromo-2-chloro-11-methyl-9-(trifluoromethyl)chromeno[2,3-b]indole (4s): Compound was
synthesized according to the General Method B. 174.1 mg (21%), yellow crystals, mp: 263 °C. IR (KBr,
cm-1): 1545 (aromatic), 1318, 1116 (CF3). 1H NMR (500 MHz, pyridine-d5): δ= 2.97 (3H, s, CH3), 7.94 (1H,
dd, J1 = 8.3 Hz, J2 = 1.2 Hz, C2-H), 7.98 (1H, d, J = 8.3 Hz, C1-H), 8.09 (1H, d, J = 2.4 Hz, C8-H), 8.13 (1H,
13
d, J = 2.4 Hz, C6-H), 8.45 (1H, brs, C4-H). C NMR (125 MHz, pyridine-d5): δ = 15.0 (C5-CH3), 112.3
(C9-Br), 120.0 (C1), 120.7 (C4), 121.5 (C5a), 122.0 (C4b), 123.3 (C3-CF3), 124.5 (C4a), 125.1 (C6), 125.3
(C3-CF3), 126.7 (C2), 129.9 (C7-Cl), 135.1 (C8), 143.9 (C5-CH3), 146.7 (C9a), 156.0 (C11a), 164.7 (C=N,
C10a). HRMS m/z calcd for C17H9BrClF3NO (M+H)+ 413.9430, found 413.9500. Anal. Calcd for
C17H8BrClF3NO: C, 49.25; H, 1.94; N, 3.38%. Found C, 49.21; H, 1.94; N, 3.13%.
2-Bromo-11-methyl-9-(trifluoromethyl)chromeno[2,3-b]indole (4t): Compound was synthesized
according to the General Method B. 159.7 mg (21%); yellow crystals, mp 244 °C. IR (KBr, cm-1): 1650
1
(C=N), 1545 (aromatic), 1320, 1154 (CF3). H NMR (500 MHz, pyridine-d5): δ = 2.94 (3H, s, C5-CH3),
7.58 (1H, d, J = 8.8 Hz, C9-H), 7.85 (1H, dd, J1 = 8.8 Hz, J2 = 2.3 Hz, C8-H), 7.92 (1H, dd, J1 = 8.2 Hz, J2 =
13
1.0 Hz, C2-H), 7.98 (1H, d, J = 8.2 Hz, C1-H), 8.28 (1H, d, J = 2.3 Hz, C6-H), 8.44 (1H, brs, C4-H). C
NMR (125 MHz, pyridine-d5): δ = 14.8 (C5-CH3), 117.4 (C7-Br), 119.6 (C9), 119.7 (C1), 120.5 (C4), 122.3
(C5a), 123.0 (C8), 123.0 (C4b), 124.2 (C3-CF3), 124.7 (C4a), 125.5 (C3-CF3), 126.3 (C2), 128.5 (C6), 144.4
(C5-CH3), 150.3 (C9a), 156.1 (C11a), 165.0 (C=N, C10a). HRMS m/z calcd for C17H10BrF3NO (M+H)+
379.9820, found 379.9888. Anal. Calcd for C17H9BrF3NO: C, 53.71; H, 2.39; N, 3.68%. Found C, 53.38; H,

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2.44; N, 3.44%.
2-Bromo-11-ethyl-9-(trifluoromethyl)chromeno[2,3-b]indole (4u): Compound was synthesized
according to the General Method B. 102.5 mg (13%), yellow crystals, mp 226 °C. IR (KBr, cm-1): 1644
(C=N), 1325, 1100 (CF3). 1H NMR (500 MHz, DMSO-d6): δ = 1.39 (3H, t, J = 7.6 Hz, CH3), 3.55 (2H, q, J
= 7.6 Hz, CH2), 7.77 (1H, d, J = 8.8 Hz, C1-H), 7.86 (1H, d, J = 8.8 Hz, C2-H), 7.86 (1H, d, J = 8.8 Hz,
C9-H), 8.01 (1H, dd, J1 = 8.8 Hz, J2 = 2.3 Hz, C8-H), 8.32 (1H, brs, C4-H), 8.47 (1H, d, J = 2.3 Hz, C6-H);
13C NMR (125 MHz, DMSO-d6): δ = 13.8 (C5-CH2CH3), 22.0 (C5-CH2CH3), 117.7 (C7-Br), 119.8 (C1),
120.5 (C4), 120.7 (C9), 121.2 (C4b), 121.4 (C5a), 123.3 (C3), 124.0 (C4a), 125.4 (C3-CF3), 126.5 (C2), 128.7
(C6), 135.8 (C8), 150.7 (C9a), 151.8 (C5-CH2CH3), 155.4 (C11a), 165.3 (C=N, C10a). HRMS m/z calcd for
C18H12BrF3NO (M+H)+ 393.9976, found 394.0059. Anal. Calcd for C18H11BrF3NO: C, 54.85; H, 2.81; N,
3.55%. Found C, 54.68; H, 2.74; N, 3.43%.
Methyl 2-methoxy-11-methylchromeno[2,3-b]indole-9-carboxylate (4v): Compound was synthesized
according to the General Method B. 359.9 mg, (56%), yellow crystals, mp 229 °C. IR (KBr, cm-1): 1704
1
(>C=O), 1248, 1186 (C-O-C). H NMR (500 MHz, pyridine-d5): δ = 2.89 (3H, s, C5-CH3), 3.83 (3H, s,
OCH3), 3.95 (3H, s, COOCH3), 7.37 (1H, dd, J1 = 9.0 Hz, J2 = 2.8 Hz, C8-H), 7.49 (1H, d, J = 2.8 Hz, C6-H),
7.63 (1H, d, J = 9.0 Hz, C9-H), 7.99 (1H, d, J = 8.3 Hz, C1-H), 8.45 (1H, dd, J1 = 8.3 Hz, J2 = 0.9 Hz, C2-H),
8.94 (1H, brs, C4-H). 13C NMR (125 MHz, pyridine-d5): δ = 14.9 (C5-CH3), 51.8 (C3-COOCH3), 55.7
(C7-OCH3), 108.4 (C6), 118.7 (C9), 118.9 (C1), 119.9 (C8), 121.3 (C5a), 122.3 (C4b), 123.8 (C3-COOMe),
124.6 (C4a), 125.0 (C4), 130.7 (C2), 145.0 (C5-CH3), 145.8 (C9a), 156.4 (C7-OCH3), 157.3 (C11a), 165.9
(C=N, C10a), 167.2 (C3-COOMe). HRMS m/z calcd for C19H16NO4 (M+H)+ 322.1001, found 322.1067.
Anal. Calcd for C19H15NO4: C, 71.02; H, 4.70; N, 4.36%. Found C, 69.74; H, 4.42; N, 4.22%.
Methyl 2-hydroxy-11-methylchromeno[2,3-b]indole-9-carboxylate (4w): Compound was synthesized
according to the General Method B. 454.8 mg, (74%); brown crystals, mp 283 °C. IR (KBr, cm-1): 1727
(>C=O), 1225 (C-O-C); 1H NMR (500 MHz, pyridine-d5): δ = 2.83 (3H, s, C5-CH3), 3.97 (3H, s, COOCH3),
7.50 (1H, dd, J1 = 8.9 Hz, J2 = 2.8 Hz, C8-H), 7.62 (1H, d, J = 8.9 Hz, C9-H), 7.65 (1H, d, J = 2.8 Hz, C6-H),
7.95 (1H, d, J = 8.3 Hz, C1-H), 8.44 (1H, dd, J1 = 8.3 Hz, J2 = 1.5 Hz, C2-H), 8.91 (1H, d, J = 1.5 Hz, C4-H),
11.93 (1H, brs, OH); 13C NMR (125 MHz, pyridine-d5): δ = 14.7 (C5-CH3), 51.6 (C3-COOCH3), 110.7 (C6),
118.6 (C9), 118.8 (C1), 121.2 (C8), 121.6 (C5a), 122.2 (C4b), 123.8 (C3-COOMe), 124.6 (C4a), 124.9 (C4),
130.6 (C2), 144.9 (C5-CH3), 145.1 (C9a), 155.5 (C7-OH), 157.5 (C11a), 166.1 (C=N, C10a), 167.2
(C3-COOMe). HRMS m/z calcd for C18H14NO4 (M+H)+ 308.0845, found 308.0914. Anal. Calcd for
C18H13NO4: C, 70.35; H, 4.26; N, 4.56%. Found C, 69.74; H, 4.16; N, 4.52%.
Methyl 4-bromo-2-chloro-11-methylchromeno[2,3-b]indole-9-carboxylate (4x): Compound was
synthesized according to the General Method B. 283.3 mg (35%), yellow crystals, mp 277 °C. IR (KBr,
cm-1): 1706 (>C=O), 1244 (C-O-C). 1H NMR (500 MHz, pyridine-d5): δ = 2.91 (3H, s, C5-CH3), 3.98 (3H,

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s, COOCH3), 7.95 (1H, d, J = 8.3 Hz, C1-H), 8.08 (1H, d, J = 2.3 Hz, C8-H), 8.09 (1H, d, J = 2.3 Hz, C6-H),
13
8.46 (1H, dd, J1 = 8.3 Hz, J2 = 1.3 Hz, C2-H), 8.91 (1H, d, J = 1.3 Hz, C4-H). C NMR (125 MHz,
pyridine-d5): δ = 14.8 (C5-CH3), 51.8 (C3-COOCH3), 112.3 (C9-Br), 119.5 (C1), 123.0 (C5a), 123.7 (C4b),
124.0 (C3-COOMe), 124.9 (C6), 125.0 (C4a), 125.3 (C4), 129.9 (C7-Cl), 131.4 (C2), 134.8 (C8), 143.0
(C5-CH3), 146.7 (C9a), 157.2 (C11a), 165.6 (C=N, C10a), 166.9 (C3-COOMe). HRMS m/z calcd for
C18H12BrClNO3 (M+H)+ 403.9611, found 403.9683. Anal. Calcd for C18H11BrClNO3: C, 53.43; H, 2.74; N,
3.46%. Found C, 53.47; H, 2.73; N, 3.20%.
Methyl 2-bromo-11-methylchromeno[2,3-b]indole-9-carboxylate (4y): Compound was synthesized
according to the General Method B. 407.2 mg (55%), yellow crystals, mp 261 °C. IR (KBr, cm-1): 1718
(>C=O), 1252 (C-O-C). 1H NMR (500 MHz, pyridine-d5): δ = 2.89 (3H, s, C5-CH3, d, J = 8.8 Hz, C9-H),
7.83 (1H, dd, J1 = 8.8 Hz, J2 = 2.3 Hz, C8-H), 7.95 (1H, d, J = 8.2 Hz, C1-H), 8.24 (1H, d, J = 2.3 Hz, C6-H),
8.45 (1H, dd, J1 = 8.2 Hz, J2 = 1.5 Hz, C2-H), 8.91 (1H, d, J = 1.5 Hz, C4-H). 13C NMR (125 MHz,
pyridine-d5): δ = 14.7 (C5-CH3), 51.7 (C3-COOCH3), 117.4 (C7-Br), 119.2 (C1), 119.6 (C9), 122.5 (C5a),
123.0 (C4b), 124.5 (C3-COOMe), 124.6 (C4a), 125.1 (C4), 128.4 (C6), 131.1 (C2), 134.7 (C8), 143.5
(C5-CH3), 150.2 (C9a), 157.3 (C11a), 165.3 (C=N, C10a), 167.0 (C3-COOMe). HRMS m/z calcd for
C18H13BrNO3 (M+H)+ 370.0001, found 370.0070. Anal. Calcd for C18H12BrNO3: C, 58.40; H, 3.27; N,
3.78%. Found C, 58.32; H, 3.24; N, 3.72%.
Methyl 2-bromo-11-ethylchromeno[2,3-b]indole-9-carboxylate (4z): Compound was synthesized
according to the General Method B. 38.4 mg (5%), yellow crystals, mp 220 °C. IR (KBr, cm-1): 1688
1
(>C=O), 1643 (C=N), 1541 (C=C); H NMR (500 MHz, DMSO-d6): δ = 1.40 (3H, t, J = 7.6 Hz,
C5-CH2CH3), 3.51 (2H, q, J = 7.6 Hz, C5-CH2CH3), 3.91 (3H, s, COOCH3), 7.69 (1H, d, J = 8.3 Hz, C1-H),
7.85 (1H, d, J = 8.8 Hz, C9-H), 8.00 (1H, dd, J1 = 8.8 Hz, J2 = 2.1 Hz, C8-H), 8.13 (1H, dd, J1 = 8.3 Hz, J2 =
1.2 Hz, C2-H), 8.45 (1H, d, J = 2.1 Hz, C6-H), 8.55 (1H, d, J = 1.2 Hz, C4-H);13C NMR (125 MHz,
DMSO-d6): δ = 13.7 (C5-CH2CH3), 22.0 (C5-CH2CH3), 52.6 (C3-COOCH3), 117.4 (C7-Br), 119.3 (C1),
120.7 (C9), 121.4 (C5a), 121.5 (C4b), 123.8 (C3-COOMe), 124.1 (C4a), 124.6 (C4), 128.6 (C6), 130.9 (C2),
135.6 (C8), 150.7 (C9a), 150.9 (C5-CH2CH3), 156.5(C11a), 165.6 (C=N, C10a), 166.8 (C3-COOMe). HRMS
m/z calcd for C19H15BrNO3 (M+H)+ 384.0157, found 384.0237. Anal. Calcd for C19H14BrNO3: C, 59.39; H,
3.67; N, 3.65%. Found C, 59.22; H, 3.48; N, 3.56%.
Chromeno[2,3-b]indole (4aa): Compound was synthesized according to the General Method C. 53 mg
(7%), yellow crystals, mp 115 °C. IR (KBr, cm-1): 1653 (>C=N), 1544 (aromatic). 1H NMR (500 MHz,
DMSO-d6): δ = 7.32 (1H, t, J = 7.5 Hz, C3-H), 7.52 (1H, t, J = 7.5 Hz, C2-H), 7.56 (1H, t, J = 8.0 Hz, C7-H),
7.59 (1H, d, J = 7.5 Hz, C1-H), 7.80 (1H, t, J = 8.0 Hz, C8-H), 7.84 (1H, d, J = 8.0 Hz, C9-H), 8.04 (1H, d, J
= 8.0 Hz, C6-H), 8.08 (1H, d, J = 7.5 Hz, C4-H), 8.85 (1H, s, C5-H) ppm. 13C NMR (125 MHz, DMSO-d6):
δ = 117.9 (C9), 119.1 (C1), 119.8 (C5a), 122.6 (C4), 123.0 (C3), 123.9 (C4a), 125.2 (C4b), 125.4 (C7), 130.3

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(C2), 130.3 (C6), 132.3 (C5), 132.7 (C8), 151.6 (C9a), 152.3 (C11a), 164.3 (C=N, C10a) ppm. HRMS m/z calcd
for C15H10NO (M+H)+ 220.0684, found 220.0756;
9-Methylchromeno[2,3-b]indole (4ab): Compound was synthesized according to the General Method B.
69.9 mg (15%); orange crystals; mp 200 °C. IR (KBr, cm-1): 2915 (C-H), 1655 (aromatic). 1H NMR (500
MHz, DMSO-d6): δ = 2.45 (3H, s, CH3), 7.33 (1H, dm, J = 8.0 Hz, C2-H), 7.46 (1H, d, J = 8.0 Hz, C1-H),
7.53 (1H, ddd, J1 = 7.8, J2 = 6.8 J3 = 1.5 Hz, C7-H), 7.78 (1H, ddd, J1 = 8.4, J2 = 6.8 J3 = 1.6 Hz, C8-H), 7.81
(1H, dm, J = 8.4 Hz, C9-H), 7.87 (1H, m, C4-H), 8.08 (1H, dd, J1 = 7.8, J2 = 1.6 Hz, C6-H), 8.75 (1H, s,
13
C5-H). C NMR (125 MHz, DMSO-d6): δ = 21.5 (CH3), 117.8 (C9), 118.8 (C1), 119.8 (C5a), 122.8 (C4),
124.0 (C4a), 125.4 (C4b), 125.2 (C7), 131.1 (C2), 130.2 (C6), 131.6 (C5), 132.5 (C8), 150.5 (C11a), 151.5 (C9a),
164.0 (C=N, C10a). HRMS m/z calcd for C16H12NO (M+H)+ 234.0919, found 234.0915.
9-Bromochromeno[2,3-b]indole (4ac): Compound was synthesized according to the General Method B.
1
166.9 mg (28%); orange crystals, mp 210 °C. IR (KBr, cm-1): 1651 (C=N), 1612 (C=C). H NMR (500
MHz, DMSO-d6): δ = 7.54 (1H, d, J = 8.4 Hz, C1-H), 7.57 (1H, ddd, J1 = 7.9 Hz, J2 = 6.6 Hz, J3 = 1.8 Hz,
C7-H), 7.66 (1H, dd, J1 = 8.4 Hz, J2 = 2.1 Hz, C2-H), 7.83 (1H, ddd, J1 = 8.4 Hz, J2 = 6.6 Hz, J3 = 1.5 Hz,
C8-H), 7.86 (1H, dd, J1 = 8.4 Hz, J2 = 1.8 Hz, C9-H), 8.03 (1H, dd, J1 = 7.9 Hz, J2 = 1.5 Hz, C6-H), 8.33 (1H,
d, J = 2.1 Hz, C4-H), 8.92 (1H, s, C5-H). 13C NMR (125 MHz, DMSO-d6): δ = 114.8 (C3-Br), 118.0 (C9),
119.7 (C5a), 121.0 (C1), 124.4 (C4b), 125.3 (C4), 125.5 (C7), 126.1 (C4a), 130.6 (C6), 132.5 (C2), 133.2 (C8),
134.1 (C5), 151.7 (C9a), 151.8 (C11a), 164.6 (C=N, C10a). HRMS m/z calcd for C15H9BrNO (M+H)+
297.9789, found 297.9868. Anal. Calcd for C15H8BrNO: C, 60.43; H, 2.70; N, 4.70%. Found C, 59.30; H,
2.73; N, 4.55%.
Chromeno[2,3-b]indole-9-carbonitrile (4ad): Compound was synthesized according to the General
Method B. 78.2 mg (16%); orange crystals; mp 326 °C. IR (KBr, cm-1): 1656 (C=N), 2221 (C≡N). 1H NMR
(500 MHz, DMSO-d6): δ = 7.62 (1H, m, C7-H), 7.76 (1H, d, J = 8.2 Hz, C1-H), 7.89 (1H, m, C8-H), 7.93
(1H, dm, J = 8.0 Hz, C9-H), 7.95 (1H, dd, J1 = 8.2 Hz, J2 = 1.7 Hz, C2-H), 8.12 (1H, dm, J = 7.8 Hz, C6-H),
13
8.62 (1H, d, J = 1.7 Hz, C4-H), 9.05 (1H, s, C5-H). C NMR (125 MHz, DMSO-d6): δ = 104.5 (C3-CN),
118.1 (C9), 119.7 (C5a), 120.1 (C1), 120.2 (CN), 123.7 (C4b), 124.6 (C4a), 125.8 (C7), 126.8 (C4), 130.8 (C6),
133.7 (C8), 133.8 (C2), 135.5 (C5), 151.9 (C9a), 156.1 (C11a), 166.7 (C=N, C10a). HRMS m/z calcd for
C16H9N2O (M+H)+ 245.0714, found 245.0710. Anal. Calcd for C16H8N2O: C, 78.68; H, 3.30; N, 11.47%.
Found C, 78.34; H, 2.91; N, 11.21%.
9-(Trifluoromethyl)chromeno[2,3-b]indole (4ae): Compound was synthesized according to the General
Method B. 57.4 mg (10%); yellow crystals, mp 268 °C. IR (KBr, cm-1): 1655 (C=N), 1323, 1157 (CF3). 1H
NMR (500 MHz, DMSO-d6): δ = 7.61 (1H, ddd, J1 = 7.8 Hz, J2 = 7.5 Hz, J3 = 1.2 Hz, C7-H), 7.77 (1H, d, J
= 8.2 Hz, C1-H), 7.85 (1H, d, J = 8.2 Hz, C2-H), 7.87 (1H, ddd, J1 = 8.0 Hz, J2 = 7.5 Hz, J3 = 1.2 Hz, C8-H),

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7.91 (1H, dd, J1 = 8.0 Hz, J2 = 1.2 Hz, C9-H), 8.07 (1H, dd, J1 = 7.8 Hz, J2 = 1.2 Hz, C6-H), 8.55 (1H, brs,
C4-H), 9.09 (1H, s, C5-H). 13C NMR (125 MHz, DMSO-d6): δ = 118.1 (C9), 119.6 (C1), 119.7 (C5a), 119.9
(C4), 123.2 (C3-CF3), 124.3 (C4a), 124.3 (C4b), 125.7 (C7), 125.8 (C3-CF3), 126.8 (C2), 130.7 (C6), 133.4
(C8), 135.0 (C5), 151.9 (C9a), 155.6 (C11a), 166.2 (C=N, C10a). HRMS m/z calcd for C16H9F3NO (M+H)+
288.0558, found 288.0629. Anal. Calcd for C16H8F3NO: C, 66.90; H, 2.81; N, 4.88%. Found C, 66.80; H,
2.98; N, 4.69%.
Methyl chromeno[2,3-b]indole-9-carboxylate (4af): Compound was synthesized according to the
General Method C. 9.4 mg (3.4%), orange crystals, mp 220 °C. IR (KBr, cm-1): 1709 (>C=O), 1103
(C-O-C). 1H NMR (500 MHz, DMSO-d6): δ = 3.91 (3H, s, OCH3), 7.60 (1H, dd, J1 = 7.8 Hz, J2 = 7.0 Hz,
C7-H), 7.69 (1H, d, J = 8.1 Hz, C1-H), 7.85 (1H, ddd, J1 = 8.1 Hz, J2 = 7.0 Hz, J3 = 1.4 Hz, C8-H), 7.89 (1H,
dm, J = 8.1 Hz, C9-H), 8.14 (1H, dd, J1 = 8.1, J2 = 1.7 Hz, C2-H), 8.04 (1H, dd, J1 = 7.8, J2 = 1.4 Hz, C6-H),
8.75 (1H, d, J = 1.7 Hz, C4-H), 9.11 (1H, s, C5-H). 13C NMR (125 MHz, DMSO-d6): δ = 52.6 (OCH3), 118.1
(C9), 119.1 (C1), 119.8 (C5a), 123.9 (C4), 124.1 (C4a), 124.5 (C4b), 125.7 (C7), 130.6 (C6), 131.3 (C2), 133.2
(C8), 134.4 (C5), 151.8 (C9a), 156.7 (C11a), 166.5 (C=N, C10a), 166.9 (C3-COOMe). HRMS m/z calcd for
C17H12NO3 (M+H)+ 278.0739, found 278.0810.
3-(2-Aminophenyl)chromen-2-one (6): Compound was synthesized according to the General Method C.
1H NMR (500 MHz, (CD3)2SO): H 6.82 (1H, t, J = 8.0 Hz, Ar-H), 6.89 (1H, d, J = 8.0 Hz, Ar-H), 7.15 (1H,
d, J = 8.0 Hz, Ar-H), 7.21 (1H, t, J = 8.0 Hz, Ar-H), 7.38 (1H, t, J = 7.8 Hz, Ar-H), 7.45 (1H, d, J = 7.8 Hz,
Ar-H), 7.63 (1H, t, J = 7.8 Hz, Ar-H), 7.74 (1H, d, J = 7.8 Hz, Ar-H), 8.03 (1H, s, Ar-H) ppm. 13C NMR
(500 MHz, (CD3)2SO): C 116.4, 117.7, 119.2, 120.0, 122.6, 124.9, 127.2, 128.9, 129.9, 131.4, 132.1, 143.0
(>C-NH2), 143.3, 153.8 (>C-O-), 160.2 (>C=O) ppm. HRMS m/z calcd for C15H12NO2 (M+H)+ 238.0789,
found = 238.0863;
3-[2-[(E)-(2-Hydroxyphenyl)methyleneamino]-5-methylphenyl]chroman-2-one (5ab): Compound
was synthesized according to the General Method B. 42.6 mg (6%); yellow crystals, mp 224 °C. IR (KBr,
cm-1): 1711 (C=N), 1613 (C=C). 1H NMR (500 MHz, DMSO-d6): δ = 2.39 (3H, s, CH3), 6.82 (1H, d, J =
8.0 Hz, Ar-H), 6.94 (1H, t, J = 8.0 Hz), 7.32 (1H, d, J = 1.5 Hz, Ar-H), 7.35 (1H, t, J = 8.0 Hz, Ar-H), 7.38
(1H, dd, J1 = 8.1, J2 = 1.5 Hz, Ar-H), 7.39 (1H, td, J1 = 7.7, J2 = 1.5 Hz, Ar-H), 7.46 (1H, d, J = 8.1 Hz,
Ar-H), 7.48 (1H, dd, J1 = 8.2, J2 = 1.5 Hz, Ar-H), 7.61 (1H, d, J = 8.0 Hz), 7.65 (1H, ddd, J1 = 8.2, J2 = 7.7
Hz, J3 = 1.5 Hz, Ar-H), 7.75 (1H, dd, J1 = 7.7 Hz, J2 = 1.5 Hz, Ar-H), 8.13 (1H, s, (C=O)C=CH-)), 8.93 (1H,
13
s, N=CH), 12.85 (1H, s, OH). C NMR (125 MHz, DMSO-d6): δ = 21.0 (C-CH3), 116.6, 117.0, 118.5,
119.5, 119.5, 119.8, 125.2, 127.6, 129.1, 131.0, 131.1, 131.6, 132.4, 133.1, 133.7, 137.0 (C-CH3), 143.0,
144.7 (>C-N), 153.8 (C-O-), 159.7 (C=O), 160.7 (C-OH), 163.4 (C=N). HRMS m/z calcd for C23H18NO3
(M+H)+ 356.1290, found 356.3820. Anal. Calcd for C23H17NO3: C, 77.73; H, 4.82; N, 3.94%. Found C,
77.24; H, 3.43; N, 3.86%.

HETEROCYCLES, Vol. 87, No. 10, 2013
2069
3-[5-Bromo-2-[(E)-(2-hydroxyphenyl)methyleneamino]phenyl]chroman-2-one (5ac): Compound was
synthesized according to the General Method C. 21 mg, (5%); yellow crystals, mp 232 °C. IR (KBr, cm-1):
1710 (>C=O), 1606 (C=N). 1H NMR (500 MHz, DMSO-d6): δ = 6.84 (1H, d, J = 8.0 Hz, Ar-H), 6.95 (1H,
t, J = 8.0 Hz, Ar-H), 7.37 (1H, t, J = 8.0 Hz, Ar-H), 7.40 (1H, td, J1 = 7.7, J2 = 1.5 Hz, Ar-H), 7.48 (1H, dd,
J1 = 8.2, J2 = 1.5 Hz, Ar-H), 7.50 (1H, d, J = 8.6 Hz, Ar-H), 7.62 (1H, d, J = 8.0 Hz, Ar-H), 7.67 (1H, ddd,
J1 = 8.2, J2 = 7.7 Hz, J3 = 1.5 Hz), 7.75 (1H, dd, J1 = 7.7, J2 = 1.5 Hz, Ar-H), 7.75 (1H, d, J = 2.3 Hz), 7.77
(1H, dd, J1 = 8.6, J2 = 2.3 Hz, Ar-H, Ar-H), 8.20 (1H, s, (C=O)C=CH-)), 8.95 (1H, s, N=CH), 12.52 (1H, brs,
OH). 13C NMR (125 MHz, DMSO-d6): δ = 116.7, 117.1, 119.4, 119.6 (C-Br), 119.7, 121.1, 125.3, 125.9,
129.2, 132.7, 133.1, 133.2, 133.2, 132.7, 133.6, 134.2, 143.8, 146.8 (>C-N), 153.8 (C-O-), 159.5 (C=O),
160.7 (C-OH), 164.8 (C=N). HRMS m/z calcd for C22H15BrNO3 (M+H)+ 420.0157, found 420.0226. Anal.
Calcd for C22H14BrNO3: C, 62.88; H, 3.36; N, 3.33%. Found C, 62.78; H, 3.29; N, 3.10%.
ACKNOWLEDGEMENTS
The authors acknowledge Barbara Balázs and Tamás Gáti for spectral measurements.
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