HETEROCYCLES

Short Paper | Regular issue | Vol. 87, No. 10, 2013, pp. 2053-2069
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, Tibor Novák, Gábor Blaskó, Imre Fejes, François Perron-Sierra, and Miklós Nyerges*

CHL, Servier Research Institute of Medicinal Chemistry, Záhony utca 7, H-1031 Budapest, Hungary

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 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

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.

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.

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 areuncorrected. 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), 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). 1H 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). 13C 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 (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). 13C 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%.
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 (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%.
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 (Ar-Br). 1H 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, d, J = 2.0 Hz, C4-H). 13C 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). 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). 13C 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, brs, OH). 13C 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 (aromatic), 1331, 1154 (CF3). 1H NMR (500 MHz, pyridine-d5): δ = 2.97 (3H, s, C5-CH3), 3.88 (3H, s, 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, C2-H), 7.98 (1H, d, J = 8.3 Hz, C1-H), 8.43 (1H, brs, C4-H), 11.97 (1H, brs, OH). 13C 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, d, J = 2.4 Hz, C6-H), 8.45 (1H, brs, C4-H). 13C 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 (C=N), 1545 (aromatic), 1320, 1154 (CF3). 1H 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). 13C 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, 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 (>C=O), 1248, 1186 (C-O-C). 1H 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, 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). 13C 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 (>C=O), 1643 (C=N), 1541 (C=C); 1H 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 (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, C5-H). 13C 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. 166.9 mg (28%); orange crystals, mp 210 °C. IR (KBr, cm-1): 1651 (C=N), 1612 (C=C). 1H 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), 8.62 (1H, d, J = 1.7 Hz, C4-H), 9.05 (1H, s, C5-H). 13C 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), 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): δH 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): δC 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, s, N=CH), 12.85 (1H, s, OH). 13C 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%.
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.

References

1. M. A. M. Massoud, Alexandria J. Pharm. Sci., 2000, 14, 51; W. B. Chen, Y. H. Liao, X. L. Du, X. M. Zhang, and W. C. Yuan, Green Chem., 2009, 11, 1465; CrossRef F. H. Havaidar and S. M. Burudkar, Indian J. Heterocycl. Chem., 2011, 21, 23.
2. A. S. Ijaz, J. Parrick, and A. Yahya, J. Chem. Res. Synop., 1990, 4, 116; F. Buzzetti, V. Pinciroli, M. G. Brasca, A. Crugnola, S. Fustinoni, and A. Longo, Gazz. Chim. Ital., 1995, 125, 69; W. Zhang and M. L. Go, Bioorg. Med. Chem., 2009, 17, 2077; CrossRef Y. Hu, H. Kang, B. W. Zeng, H. Huang, and P. Wei, Heterocycl. Commun., 2008, 14, 263; CrossRef K. Islam, H. F. Chin, A. O. Olivares, L. P. Saunders, E. M. De La Cruz, and T. M. Kapoor, Angew. Chem. Int. Ed., 2010, 49, 8484; CrossRef L. Sun, N. Tran, F. Tang, H. App, P. Hirth, G. McMahon, and C. Tang, J. Med. Chem., 1998, 41, 2588. CrossRef
3. R. A. Abramovitch and D. H. Hey, J. Chem. Soc., 1954, 1697. CrossRef
4. F. Eiden and H. Dobinsky, Synthesis, 1970, 365; CrossRef F. Eiden and H. Dobinsky, Justus Liebigs Ann. Chem., 1975, Volume Date 1974, 12, 1981; R. Engqvist and J. Bergman, Tetrahedron, 2003, 59, 9649. CrossRef
5. W. Loewe, S. Witzel, S. Tappmeyer, and R. Albuschat, J. Heterocycl. Chem., 2004, 41, 317. CrossRef