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

DOI: 10.3987/COM-13-12780

Source and publish data:

Heterocycles p. 2053 - 2069 (2013)

Update date:2022-08-04

Topics:

Authors:

Graczol-Foerdos, Eszter

Novak, Tibor

Blasko, Gabor

Fejes, Imre

Perron-Sierr, Francoise

Nyerges, Miklos

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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,^aTibor Novák,^aGábor Blaskó,^aImre Fejes,^a

Françoise Perron-Sierra,^band Miklós Nyerges^a,*

^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.¹The

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 80^thbirthday.

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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,³while a few closely related chromono[2,3-b]indoles have

been prepared from the corresponding 3-(2-hydroxybenzoyl)oxindoles⁴or, in one case, via an

aminoisoflavone – salicyloylindole ring transformation.⁵

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.

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Table 1

Entry

R¹

R²

R³

R⁴

Method^a3 (%)^b

4% (%)^b

(76)

(53)

OMe

3c (60)

4d 85 (39)^d

4e 79 (15)^c

4f 94 (72)^c

4g 63 (28)^c

4h 86 (45)^d

4i 47 (9)^e

OMe

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

OMe

CF₃

CO₂Me

OMe

^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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Table 2

Entry

5 or 6%

(%)^b

R¹

R⁴Method^a

3% (%)^b

4% (%)^b

3aa 30 (26)^d

3aa 52 (35)^d

3ab 45 (40)^c4ab 21 (15)^d

3ab 8 (8)^d

4aa 37 (7)^d

6aa 2 (2)

5ab 13 (6)^d

4ac 30 (28)^d

5ac 32 (5)^d

CF₃

3ad 61 (58)^d4ad 20 (16)^d

3ae 17 (15)^d

3af 37 (26)^d

4ae 10 (10)^d

CO₂Me OH

4af 13 (3.4)^d

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.

-H₂O

Scheme 2

HETEROCYCLES, Vol. 87, No. 10, 2013

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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-d₅using 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

(-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

(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,

>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 (C_5a), 122.2 (C_4b), 122.4 (C₃),

124.0 (C₄), 124.4 (C_4a), 129.3 (C₂), 144.4 (CCH₃), 145.5 (C_9a), 152.6 (C_11a), 156.2 (COCH₃), 163.7 (C_10a).

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 (C_5a), 123.4 (C_4b), 124.0 (C₄), 125.0 (C_4a), 130.0 (C₂), 131.3 (C₃-CH₃), 142.0 (C₅-CH₃),

145.8 (C_9a), 151.6 (C_11a), 156.2 (COCH₃), 163.7 (C=N, C_10a). 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 (C_5a), 123.1 (C_4b), 124.0 (C₄),

125.0 (C_4a), 129.9 (C₂), 131.1 (C₃-CH₃), 142.2 (C₅-CH₃), 145.0 (C_9a), 151.6 (C_11a), 155.1 (C₇-OH), 163.9

(C=N, C_10a). 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 (C_5a), 124.0 (C_4b), 124.3

(C₄), 124.9 (C_4a), 128.1 (C₆), 130.4 (C₂), 131.9 (C₃-CH₃), 133.9 (C₈), 140.7 (C₅-CH₃), 150.2 (C_9a), 151.4

(C_11a), 163.1 (C=N, C_10a). 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 (C_5a), 122.3 (C₄), 122.3 (C_4b), 125.1 (C_4a), 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 (C_9a),

152.1 (C_11a), 156.3 (COCH₃), 164.0 (C_10a). 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 (C_5a), 122.1 (C₄), 122.3 (C_4b), 124.5 (C_4a), 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 (C_9a), 152.1 (C_11a), 163.9

(C_10a). 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 (C_4b), 121.3 (C_5a), 126.3 (C₄), 126.3 (C_4a), 131.7 (C₂), 145.8 (C_9a), 146.8 (C₅-CH₃), 151.5 (C_11a),

156.4 (COCH₃), 163.8 (C=N, C_10a). 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

(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 (C_4b), 121.3 (C_5a),

121.4 (C₈), 126.1 (C₄), 126.3 (C_4a), 131.5 (C₂), 144.7 (C_9a), 146.6 (C₅-CH₃), 151.5 (C_11a), 154.6 (C₇-OH),

163.9 (C=N, C_10a). 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,

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 (C_5a), 122.0 (C_4b), 126.1 (C₆), 126.3 (C_4a), 126.7 (C₄), 129.5 (C₇-Cl), 132.5 (C₂), 135.0

(C₈), 145.4 (C₅-CH₃), 146.7 (C_9a), 151.2 (C_11a), 164.7 (C=N, C_10a). 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 (C_4b), 122.6 (C_5a), 126.4 (C_4a), 126.5

(C₄), 129.2 (C₆), 132.1 (C₂), 135.4 (C₈), 145.8 (C₅-CH₃), 150.3 (C_9a), 151.4 (C_11a), 163.5 (C=N, C_10a).

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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,

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 (C_5a), 121.5 (C_4b), 125.0 (C_4a), 127.3 (C₄), 132.5

(C₂), 146.0 (C_9a), 146.4 (C₅-CH₃), 156.5 (C_11a), 156.7 (COCH₃), 163.9 (C=N, C_10a). 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,

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 (C_4b), 121.4 (C_5a), 122.0 (C₈), 124.9 (C_4a), 127.9 (C₄), 132.8 (C₂), 144.9

(C_9a), 148.4 (C₅-CH₃), 154.9 (C₇-OH), 155.8 (C_11a), 163.9 (C=N, C_10a). 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 (C_4b), 122.3 (C_5a), 125.0 (C_4a), 127.5 (C₄), 128.6 (C₆),

133.0 (C₂), 135.2 (C₈), 145.2 (C₅-CH₃), 150.3 (C_9a), 156.4 (C_11a), 165.4 (C=N, C_10a). 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

(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 (C_5a), 122.1 (C_4b), 123.4 (C₃-CF₃), 124.7 (C_4a), 125.6 (C₃-CF₃), 125.8 (C₂),

145.6 (C₅-CH₃), 146.0 (C_9a), 156.2 (C_11a), 156.6 (COCH₃), 165.5 (C=N, C_10a). 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,

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 (C_5a),

121.8 (C_4b), 123.1 (C₃), 124.8 (C_4a), 125.7 (C₂), 125.7 (C₃-CF₃), 145.1 (C_9a), 145.7 (C₅-CH₃), 155.5

(C₇-OH), 156.2 (C_11a), 165.7 (C=N, C_10a). 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,

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 (C_5a), 122.0 (C_4b), 123.3 (C₃-CF₃), 124.5 (C_4a), 125.1 (C₆), 125.3

(C₃-CF₃), 126.7 (C₂), 129.9 (C₇-Cl), 135.1 (C₈), 143.9 (C₅-CH₃), 146.7 (C_9a), 156.0 (C_11a), 164.7 (C=N,

C_10a). 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

(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=

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

(C_5a), 123.0 (C₈), 123.0 (C_4b), 124.2 (C₃-CF₃), 124.7 (C_4a), 125.5 (C₃-CF₃), 126.3 (C₂), 128.5 (C₆), 144.4

(C₅-CH₃), 150.3 (C_9a), 156.1 (C_11a), 165.0 (C=N, C_10a). 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 (C_4b), 121.4 (C_5a), 123.3 (C₃), 124.0 (C_4a), 125.4 (C₃-CF₃), 126.5 (C₂), 128.7

(C₆), 135.8 (C₈), 150.7 (C_9a), 151.8 (C₅-CH₂CH₃), 155.4 (C_11a), 165.3 (C=N, C_10a). 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

(>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 (C_5a), 122.3 (C_4b), 123.8 (C₃-COOMe),

124.6 (C_4a), 125.0 (C₄), 130.7 (C₂), 145.0 (C₅-CH₃), 145.8 (C_9a), 156.4 (C₇-OCH₃), 157.3 (C_11a), 165.9

(C=N, C_10a), 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 (C_5a), 122.2 (C_4b), 123.8 (C₃-COOMe), 124.6 (C_4a), 124.9 (C₄),

130.6 (C₂), 144.9 (C₅-CH₃), 145.1 (C_9a), 155.5 (C₇-OH), 157.5 (C_11a), 166.1 (C=N, C_10a), 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),

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 (C_5a), 123.7 (C_4b),

124.0 (C₃-COOMe), 124.9 (C₆), 125.0 (C_4a), 125.3 (C₄), 129.9 (C₇-Cl), 131.4 (C₂), 134.8 (C₈), 143.0

(C₅-CH₃), 146.7 (C_9a), 157.2 (C_11a), 165.6 (C=N, C_10a), 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-CH_3,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 (C_5a),

123.0 (C_4b), 124.5 (C₃-COOMe), 124.6 (C_4a), 125.1 (C₄), 128.4 (C₆), 131.1 (C₂), 134.7 (C₈), 143.5

(C₅-CH₃), 150.2 (C_9a), 157.3 (C_11a), 165.3 (C=N, C_10a), 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

(>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 (C_5a), 121.5 (C_4b), 123.8 (C₃-COOMe), 124.1 (C_4a), 124.6 (C₄), 128.6 (C₆), 130.9 (C₂),

135.6 (C₈), 150.7 (C_9a), 150.9 (C₅-CH₂CH₃), 156.5(C_11a), 165.6 (C=N, C_10a), 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 (C_5a), 122.6 (C₄), 123.0 (C₃), 123.9 (C_4a), 125.2 (C_4b), 125.4 (C₇), 130.3

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(C₂), 130.3 (C₆), 132.3 (C₅), 132.7 (C₈), 151.6 (C_9a), 152.3 (C_11a), 164.3 (C=N, C_10a) 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,

C₅-H). C NMR (125 MHz, DMSO-d₆): δ = 21.5 (CH₃), 117.8 (C₉), 118.8 (C₁), 119.8 (C_5a), 122.8 (C₄),

124.0 (C_4a), 125.4 (C_4b), 125.2 (C₇), 131.1 (C₂), 130.2 (C₆), 131.6 (C₅), 132.5 (C₈), 150.5 (C_11a), 151.5 (C_9a),

164.0 (C=N, C_10a). 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.

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 (C_5a), 121.0 (C₁), 124.4 (C_4b), 125.3 (C₄), 125.5 (C₇), 126.1 (C_4a), 130.6 (C₆), 132.5 (C₂), 133.2 (C₈),

134.1 (C₅), 151.7 (C_9a), 151.8 (C_11a), 164.6 (C=N, C_10a). 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),

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 (C_5a), 120.1 (C₁), 120.2 (CN), 123.7 (C_4b), 124.6 (C_4a), 125.8 (C₇), 126.8 (C₄), 130.8 (C₆),

133.7 (C₈), 133.8 (C₂), 135.5 (C₅), 151.9 (C_9a), 156.1 (C_11a), 166.7 (C=N, C_10a). 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 (C_5a), 119.9

(C₄), 123.2 (C₃-CF₃), 124.3 (C_4a), 124.3 (C_4b), 125.7 (C₇), 125.8 (C₃-CF₃), 126.8 (C₂), 130.7 (C₆), 133.4

(C₈), 135.0 (C₅), 151.9 (C_9a), 155.6 (C_11a), 166.2 (C=N, C_10a). 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 (C_5a), 123.9 (C₄), 124.1 (C_4a), 124.5 (C_4b), 125.7 (C₇), 130.6 (C₆), 131.3 (C₂), 133.2

(C₈), 134.4 (C₅), 151.8 (C_9a), 156.7 (C_11a), 166.5 (C=N, C_10a), 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): _H6.82 (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): _C116.4, 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,

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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