HETEROCYCLES

Communication | Special issue | Vol. 80, No. 2, 2010, pp. 831-840
Received, 31st July, 2009, Accepted, 4th September, 2009, Published online, 10th September, 2009.
DOI: 10.3987/COM-09-S(S)99

■ Nucleophilic Addition of Hetaryllithium Compounds to 3-Nitro-1-(phenylsulfonyl)indole: Synthesis of Tetracyclic Thieno[3,2-c]-δ-carbolines

Philip E. Alford, Tara L. S. Kishbaugh, and Gordon W. Gribble*

Department of Chemistry, Dartmouth College, 6128 Burke Laboratory, Hanover,
New Hampshire 03755, U.S.A.

Abstract

3-Nitro-1-(phenylsulfonyl)indole undergoes addition of aryl- and hetaryllithium nucleophiles to produce 2-substituted-3-nitroindoles. Mild reductive–acylation provides excellent access to 3-amido-2-hetarylindoles from which new thieno[3,2-c]-δ-carbolines are synthesized by cyclodehydration.

The biochemical ubiquity and medicinal success of the indole motif has earned this substructure ‘privileged’ status in drug discovery and a deep history of investigation stretching well over a century.1 Typical of π-excessive heteroaromatics, the literature of indole is characterized by electrophilic substitution.2 Reversal of this traditional reactivity offers an opposite and complementary utility; the conception of electrophilic indole has captured the imagination of several groups.3 Early pioneers employed a complicit leaving group at N-1 to facilitate a formal SN2’ by attack at C-3.4 The chemistry of 1-hydroxyindole has proven to be a versatile methodology4b that continues to yield new applications,4c though the substitution itself remains particularly specialized. Arylsulfonyl groups provide a flexible5 and accessible alternative in exchange for greatly attenuated reactivity. Although 1-(phenylsulfonyl)indole does not engage in SNAr, if augmented with powerful withdrawing groups, the polarizable indole double bond becomes receptive to a variety of nucleophiles.6

During our first survey of highly deactivated 3-nitro-1-(phenylsulfonyl)indole (1) we observed the direct addition of diethyl malonate anion to furnish the trans-dihydroindole product.6a Due to the conventional nucleophilicity of indole, formation of carbon-carbon bonds at C-2 often relies on α-lithiation7 and is limited to electrophilic reagents; 2-hetarylindoles with π-excessive hetaromatics are especially inaccessible without the use of precious metals.8 We now report our investigation of nucleophilic addition to 3-nitro-1-(phenylsulfonyl)indole (1) using hetaryllithium compounds as a means of effecting arylation at C-2. In contrast with our initial enolate example,6a conjugate addition of aryllithium produces the unprotected 2-aryl-3-nitroindole (Scheme 1). Access to 2-hetaryl substituted indoles has allowed us to synthesize the previously unknown tetracyclic hetero[3,2-c]-δ-carboline ring system.

The relatively obscure δ-carboline system is represented in only a handful of natural products, predominantly the indoloquinoline alkaloids of Cryptolepis sanquinolenta.9 While the extensive biological activity of the cryptolepine family encompasses antibacterial,10a antiplasmodial,10b antihyperglycemic,10c antimuscarinic,10d and anti-inflammatory activity,10e synthetic benzo-δ-carbolines have primarily been investigated as antimalarial and anticancer agents.11 Isomeric and analogous systems attract much of the same focus.12 Despite a renewed interest in novel heterocyclic ring structures, reported new systems average fewer than 10 per year.13 The first thieno-δ-carboline (4), synthesized in 2006 as an ellipticine analogue, has found success as a photosensitizer against human tumor cells.14 The indolo[3,2-b]thieno[2,3-d]pyridine system (5), isoelectronic with a score of biologically active compounds, represents a novel ring system.

Synthesis of 2-aryl and 2-hetaryl-3-nitroindoles
Conjugate addition of hetaryllithium and aryllithium compounds to 3-nitro-1-(phenylsulfonyl)indole6a (1) furnished 2-substituted-3-nitroindoles 6-13. Addition is presumed to proceed in a Michael fashion producing a stabilized carbanion at C-3 (Scheme 2). Tandem loss of phenylsulfinate was prompt in most cases and resulted in exclusive formation of the indole product (Table 1).

N-Protected pyrrolyllithium and indolyllithium nucleophiles (Table 2) produced mixtures of indole and indoline products. Pyrrolylindole 8 was accompanied by a small amount of indoline product (9%) which was minimized by long reaction times. Formation of indolines 14b-15b could be due in part to stabilization of the intermediate lithium nitronate by the newly incorporated protecting group. Addition of carboxylate protected indole gave indoline 15b as the major product.

Synthesis of tetracyclic δ-carbolines
Huang-Hsinmin and Mann demonstrated that 5-methylindolo[3,2-c]quinoline (17) could be generated from 3-acetamido-2-phenylindole by a Bischler-Napieralski reaction, although in low yield.16 To confirm our structure, we synthesized known acetamide 16 by extension of our earlier work.17 Classical Bischler-Napieralski conditions18 furnished 17 in yields comparable to earlier methods.16

Since many hetero[c]-δ-carbolines represent novel ring systems, we investigated the above sequence as a route to these structures. Reductive-acylation of 2-hetaryl-3-nitroindoles proceeded readily at room temperature to afford 3-acylaminoindoles 18-21; zinc metal was used to excellent effect in preference over indium, tin, or iron. The advantage of such mild conditions is readily apparent in the case of the labile furan and N-BOC pyrrole groups.

Bischler-Napieralski reaction of 20-21 successfully produced the corresponding δ-carbolines in higher yields than the phenyl precedent. While previous work suggested difficulties with cyclodehydrations of this type due to the unprotected indole nitrogen,16 hetaromatics 18-21 are more activated substrates. Though our pyrrole 18 and furan 19 substrates gave complex mixtures under these conditions, thiophenes 20-21 were more tolerant and afforded good yield of tetracyclic thieno[3,2-c]-δ-carbolines 22-23.

In conclusion, we report a method for the hetarylation of 3-nitroindoles at C-2 by nucleophilic addition of hetaryllithium compounds to 3-nitro-1-(phenylsulfonyl)indole. Reductive acylation of the resulting 3-nitro-2-hetarylindoles proceeds in high yields. A subsequent Bischler-Napieralski cyclodehydration provides examples of the previously unknown thieno[3,2-c]-δ-carboline ring system.

ACKNOWLEDGEMENTS
This work was supported by the Donors of the Petroleum Research Fund (PRF), administered by the American Chemical Society, and by Wyeth.

References

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19. Representative procedure: A solution of thiophene (0.05 mL, 52.6 mg, 0.63 mmol) in dry THF (5 mL) at -78 ˚C was treated with a lithium diisopropylamide (2.0 M in THF, 0.35 mL, 0.70 mmol) and stirred for 1 h. A solution of 3-nitro-1-(phenylsulfonyl)indole (0.160 g, 0.530 mmol) in dry THF (3 mL) was added dropwise and the mixture was stirred at -78 ˚C for 2 h and then allowed to warm to RT overnight. The reaction was quenched with water, neutralized with 10% aqueous NH4Cl, and the separated aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic extracts were washed with water, brine, dried over MgSO4, and then concentrated by rotary evaporation. Purification by column chromatography on silica gel (2:1 Hexanes:DCM) produced a bright yellow solid which recrystallized from MeOH:Et2O to form yellow crystals of 6 (78 mg, 60%).
3-Nitro-2-(thien-2-yl)indole (6): bright yellow crystals; mp 246-247˚ C; 1H NMR (CDCl3) d 9.50 (s, br, 1H), 8.40 (d, J = 8.3 Hz, 1H), 7.90 (d, J = 3.3 Hz, 1H), 7.67 (d, J = 1.3 Hz, 1H), 7.39-7.46 (m, 3H), 6.72 (m, 1H); 13C NMR (CDCl3) δ 145.0, 143.9, 133.4, 130.6, 125.7, 124.5, 122.4, 121.8, 118.7, 117.1, 113.8, 111.6; HRMS (ESI) m/z calcd for C12H19N2O2S (MH+) 245.0385, found 245.0383.
2-(Furan-2-yl)-3-nitroindole (7): bright yellow crystals; mp 230-231 ˚C (decomp); 1H NMR (CDCl3) ∂ 9.25 (s, br, 1H) 8.41-8.43 (d, J = 6.9 Hz, 1H), 8.04 (d, J = 3.8 Hz, 1H), 7.68 (d, J = 1.6 Hz, 1H), 7.28-7.47 (m, 3H), 6.72-6.73 (m, 1H); 13C NMR (DMSO) δ 147.0, 144.0, 134.7, 131.1, 125.8, 124.7, 123.7, 122.1, 120.9, 118.4, 114.0, 113.6; HRMS (ESI) m/z calcd for C12H9N2O3 (MH+) 229.0608, found 229.0613.
3-Nitro-2-(thiazol-2-yl)indole (8): yellow crystals; 223-224 °C (decomp); 1H NMR (CD3COCD3) δ 12.2 (s, br, 1H), 8.31 (dd, J = 1.5, 7.0 Hz, 1H), 8.16 (d, J = 3.0 Hz, 1H), 8.04 (d, J = 3.0 Hz, 1H), 7.77 (dd, J = 1.5, 7.0 Hz, 1H), 7.45-7.48 (m, 2H); 13C NMR (CD3COCD3) δ 154.5, 143.9, 134.3, 126.2, 125.1, 124.5, 121.9, 121.1, 113.3, 113.2; HRMS (ESI) m/z calcd for C11H8N3O2S (MH+) 246.0341, found 246.0337.
2-(1-Methylimidazol-2-yl)-3-nitroindole (9): yellow crystals; mp 258-261 ˚C (decomp); 1H NMR (CDCl3) δ 13.62 (s, br, 1H) 8.33 (d, J = 7.8 Hz, 1H), 7.25-7.42 (m, 4H), 7.19 (s, 1H) 3.78 (s, 3H); 13C NMR (DMSO) δ 137.9, 134.6, 131.1, 129.6, 127.2, 125.9, 125.0, 125.0, 121.3, 120.8, 113.9, 34.3; HRMS (ESI) m/z calcd for C12H11N4O2 (MH+) 243.0882, found 243.0882.
tert-Butyl 2-(3-nitro-indol-2-yl)-pyrrole-1-carboxylate (10): bright yellow crystals, 124-128˚C (decomp); 1H NMR (CDCl3) δ 8.88 (s, br, 1H), 8.32 (d, J = 8.3 Hz, 1H), 7.52 (m, 1H), 7.30-7.48 (m, 3H), 6.53 (dd, J = 1.7, 3.4, 1H), 6.31 (t, J = 3.4, 1H), 1.64 (s, 9H); 13C NMR (CDCl3) δ 148.8, 133.5, 132.9, 129.8, 129.3, 125.2, 125.1, 124.5, 121.8, 121.7, 121.3, 111.8, 111.0, 85.0, 27.7; HRMS (ESI) m/z calcd for C17H18N3O4 (MH+) 328.1297, found 328.1296.
tert-Butyl 2-(3-nitro-indolin-2-yl)-pyrrole-1-carboxylate (10b): light yellow solid; 145-146˚C (decomp); 1H NMR (CD3COCD3) 7.98 (d, J = 6.4 Hz, 2H), 7.83 (d, J = 8.3 Hz, 1H), 7.68 (m, 1H), 7.54-7.61 (m, 3H), 7.46 (d, J = 7.6 Hz, 1H), 7.28 (m, 1H), 7.15 (td, J = 7.6, 1.0 Hz, 1H), 6.35 (s, 1H), 6.33 (1H, m), 6.14 (1H, t, 3.4 Hz), 1.62 (9H, s); 13C NMR (CD3COCD3) 149.4, 143.2, 138.0, 134.1, 132.6, 131.3, 129.5, 128.0, 126.8, 125.1, 124.8, 122.8, 115.4, 113.1, 110.7, 89.2, 85.1, 64.7, 27.4.
3-Nitro-2-(pyridin-2-yl)indole (11): yellow solid; mp 202-204 °C (decomp); 1H NMR (CDCl3) δ 10.48 (br s, 1H), 8.68-8.71 (m, 2H), 8.39 (d, 1H, 7 Hz), 7.91 (m, 1H), 7.46 (m, 1 H), 7.39-7.43 (m, 3H); 13C (CDCl3) δ 149.6, 147.2, 141.0, 137.8, 137.1, 133.2, 126.4, 126.1, 125.3, 124.9, 123.6, 122.3, 112.4; IR (film) 3455, 1477, 1361, 1216 cm-1; UV (EtOH) λ max 276, 364 nm; HRMS (ESI) m/z calcd for C13H10N3O2 (MH+) 240.0773, found 240.0784.
3-Nitro-2-(pyridin-3-yl)indole (12): mp 206-209 ˚C; 1H NMR (CDCl3) ∂ 13.05 (s, 1H), 8.94 (d, 1H, J = 1.7 Hz), 6.74 (dd, 1H, J = 1.7, 4.9 Hz), 8.17-8.22 (m, 2H), 7.57-7.61 (m, 2H), 7.39-7.43 (m, 2H); 13C NMR (CD3OD) ∂ 150.0, 150.0, 145.1, 142.3, 140.6, 137.7, 130.2, 128.6, 128.1, 125.8, 125.8, 125.8, 118.0, 107.8; HRMS (ESI) m/z calcd for C13H10N3O2 (MH+) 240.0773, found 240.0781.
3-Nitro-2-phenylindole (13): yellow crystals; mp 237-238 ˚C; 1H NMR (CD3COCD3) ∂ 11.62 (s, br, 1H), 8.27 (d, J = 7.6 Hz, 1H), 7.81 (m, 2H), 7.60 (d, J = 7.8 Hz, 1H), 7.57 (m, 3H), 7.40 (m, 2H); 13C (CD3COCD3) ∂ 141.5, 1234.2, 130.5, 130.2, 120.1, 128.5, 128.0, 124.7, 124.0, 122.3, 120.8, 112.7; HRMS (ESI) m/z calcd for C14H11N2O2 (MH+) 239.0821, found 239.0831.
2-(1’-(Phenylsulfonyl)indol-2’-yl)-3-nitroindole (14a): bright yellow crystals; mp 226-227 °C; 1H (CD3COCD3) δ 12.1 (s, br, 1H), 8.30-8.33 (m, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.67-7.71 (m, 4H), 7.62 (t, J = 7 Hz, 1H), 7.45-7.50 (m, 5H), 7.35 (t, J = 8 Hz, 1H) 7.28 (s, 1H); 13C (CD3COCD3) δ 138.4, 138.3, 135.3, 130.6, 130.3, 129.8, 127.7, 127.1, 125.94, 125.92, 125.91, 125.3, 125.1, 125.0, 122.9, 122.2, 121.4, 117.5, 116.1, 113.6; IR (film) 3277, 2911, 1444, 1367, 1172, 744 cm-1; UV (EtOH) λ max 256, 364 nm; HRMS m/z calcd for C22H15N3O4S (M+) 417.0783, found 417.0785.
trans-2-(1’-(Phenylsulfonyl)indol-2’-yl)-3-nitro-1-(phenylsulfonyl)indoline (14b): clear colorless crystals; mp 185-186 °C; 1H (CDCl3) δ 8.13 (d, J = 8 Hz, 1H) 7.94-7.99 (m, 4 H), 7.88 (d, J = 8 Hz, 1H), 7.50-7.79 (m, 9H), 7.23-7.38 (m, 2H), 7.14 (t, J = 7 Hz, 1H), 7.00 (m, 1H), 6.81 (m, 1H), 5.93 (s, 1H); 13C NMR (CDCl3) δ 142.5, 137.9, 137.8, 137.2, 136.6, 134.6, 134.3, 132.7, 129.7, 129.4, 129.1, 127.9, 127.1, 126.8, 125.8, 124.6, 124.4, 121.7, 115.5, 114.8, 113.0, 89.3, 64.5; HRMS (EI) calcd for C28H21N2O4S2 (M+ -HNO2) 512.0864, found 512.0874.
trans-2-(Indol-2’-yl)-3-nitro-1-(phenylsulfonyl)indoline (15b): colorless crystals; mp 156-158 ˚C; 1H NMR (CDCl3) δ 10.41 (s, br, 1H), 7.88 (m, 3H), 7.61 (m, 3H), 7.54 (d, J = 7.8 Hz, 1H), 7.43-7.5 (m, 3H), 7.24 (t, J = 7.6, 1H), 7.15 (t, J = 7.1, 1H), 7.06 (t, J = 7.1, 1H), 6.58 (s, 1H), 6.45 (s, 1H), 6.23 (s, 1H); 13C NMR (DMSO) δ 142.9, 137.6, 137.3, 135.1, 134.2, 132.7, 129.5, 128.2, 128.2, 127.7, 125.2, 124.9, 122.5, 120.7, 120.0, 116.3, 111.8, 101.0, 89.3, 63.7; HRMS (ESI) calcd for C22H18N3O4S (MH+) 420.1018, found 420.1033.
General Procedure for Reductive Acylation: A solution of 3-nitro-2-(thien-2-yl)indole (0.256 g, 1 mmol) in MeOH (5 mL) was treated with acetic anhydride (513 mg, 5 mmol), and zinc dust (0.327 g, 5 mmol). The bright yellow mixture was stirred at room temperature and monitored by TLC. The solution become clear and nearly colorless by completion. The mixture was filtered and the solvent was removed by rotary evaporation. The resulting oil was neutralized with sat. aqueous NaHCO3, extracted with EtOAc (3 x 100 mL), washed with brine, dried over MgSO4, and concentrated in vacuo. The resulting gray crude solid was purified by column chromatography (1:2 EtOAc/Hexanes) to yield white crystals (236 mg, 92%). Recrystallization from methanol produced a mixture of rotomers characteristic of these compounds.16
N-(2-Phenyl-1H­-indol-3-yl)acetamide (16): colorless crystals, 190-192˚C; major isomer: 1H NMR (CD3COCD3) δ 10.60 (s, br, 1H), 9.29 (s, 1H), 8.16 (d, J = 7.1 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.51-7.93 (m, 2H), 7.42 (t, J = 8.1 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.17 (t, J = 7.1 Hz, 1H), 7.07 (t, J = 7.3, 1H), 1.31 (s, 1.31); 13C NMR (CD3OD) δ 170.3, 137.7, 134.0, 133.4, 129.2, 126.7, 125.3, 125.1, 123.4, 121.7, 118.3, 113.8, 110.0, 21.7; HRMS (ESI) m/z calcd for C16H14N2O (M+) 250.11062, found 250.10993.
tert-Butyl 2-(3-acetamido-1H-indol-2-yl)-pyrrole-1-carboxylate (18): clear colorless crystals, 128-131˚C (decomp); major isomer: 1H NMR (CD3COCD3) 10.23 (s, 1H), 8.47 (s, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.43 (m, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.1 Hz, 1H), 7.01 (t, J = 7.1 Hz, 1H), 6.45 (m, 1H), 6.29 (t, J = 3.4 Hz, 1H), 2.06 (s, 3H), 1.31 (s, 9H); 13C NMR (CD3OD) 172.4, 149.3, 134.8, 125.7, 124.4, 123.9, 122.9, 121.9, 118.9, 118.2, 116.9, 111.7, 110.9, 110.6, 83.7, 26.7, 21.2; HRMS (ESI) m/z calcd for C19H22N3O3 (MH+) 340.1661, found 340.1659.
N-(2-(Furan-2-yl)-1H­-indol-3-yl)acetamide (19): colorless crystals, 183-185 ˚C; major isomer: 1H NMR (CD3OD) δ 10.55 (s), 8.68 (s), 7.65 (d, J = 1.2 Hz, 1H), 7.47 (d, J = 7.8 Hz, 1H) 7.40 (d, J = 8.3 Hz, 1H), 7.13 (t, J = 7.1 Hz, 1H), 7.03 (t, J = 7.1 Hz, 1H), 6.77 (d, J = 3.4 Hz, 1H), 6.60 (dd, J = 1.7 Hz, 3.4 Hz, 1H), 2.23 (3H, s) 13CNMR (CD3OD) δ 172.3, 146.7, 142.1, 135.2, 125.5, 124.0, 122.4, 119.6, 117.9, 111.5, 111.2, 108.8, 107.0, 21.5; HRMS (EI) m/z calcd for C14H12N2O2 (M+) 240.008988, found 240.09005.
N-(2-(Thiophen-2-yl)-1H­-indol-3-yl)acetamide (20): colorless crystals; 198-199˚C; major isomer: 1H NMR (DMSO-d6) δ 11.46 (s, 1H), 9.38 (s, 1H), 7.58, (d, J = 4.2 Hz, 1H), 7.54 (d, J = 3.7 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 7.17 (m, 1H), 7.11 (t, J = 8.0 Hz, 1H), 6.99 (d, J = 7.3 Hz, 1H), 2.12 (s, 3H); 13C NMR (CD3OD) δ 173.2, 135.3, 133.3, 128.1, 127.0, 126.0, 125.5, 124.0, 122.5, 119.7, 117.6, 111.1, 109.2, 21.7 HRMS (ESI) m/z calcd for C14H13N2OS (MH+) 257.0749, found 257.0760.
N-(2-(Thiophen-2-yl)-1H­-indol-3-yl)benzamide (21): colorless crystals, 195-197˚C; major isomer: 1H NMR (CD3COCD3) δ 10.68 (s, 1H), 9.18 (s, 1H), 8.20 (d, J = 7.0, 2H), 7.64 (m, 1H), 7.57-7.63 (m, 3H), 7.49 (m, 2H), 7.34 (m, 1H), 7.13-7.16 (m, 2H), 7.06 (m, 1H), 13C NMR (CD3OD) δ 169.8, 135.4, 134.6, 133.4, 133.4, 131.9, 128.6, 127.8, 127.0, 126.3, 125.5, 124.0, 122.5, 119.7, 117.8, 111.1, 109.5; HRMS (ESI) m/z calcd for C19H15N2OS (MH+) 319.0905, found 319.0913.
Representative Procedure for the Bischler-Naperalski reaction: A solution of 3-acetamido-2-(thien-2-yl)indole (50 mg, 0.20 mmol) in chloroform (3 mL) was treated with POCl3 (0.02 mL) 30 mg, 0.21 mmol) and refluxed for 1 d while being intermittently monitored by TLC. The solvent was removed in vacuo and the resulting red residue was quenched with water then neutralized with Na2CO3. The mixture was extracted with EtOAc (3 x 50 mL), washed with brine, dried over MgSO4, then concentrated in vacuo. The resulting red oil was purified by column chromatography (1:3 EtOAc/Toluene) to yield an orange-yellow solid. Recrystallization from MeOH produced white crystals of 22 (38.5 mg, 81% yield).
5-Methyl-11H-indolo[3,2-c]isoquinoline (17): white crystals, mp 244-245˚C, 1H NMR (CD3COCD3) 11.23 (s, br, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.37 (d, J = 8.2 Hz, 1H), 8.28 (d, J = 7.8 Hz, 1H), 7.87 (t, J = 7.1, 1H), 7.71 (t, J = 8.1, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.45 (t, J = 8.2 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 3.07 (s, 3H); 13C NMR (CD3COCD3) spots 150.5, 142.4, 137.6, 132.8, 129.7, 127.2, 126.0, 125.5, 125.4, 121.5, 119.9, 119.6, 116.7, 111.8, 110.0, 30.0; HRMS (EI) m/z calcd for C16H12N2 (M+) 232.09938, found 232.10005.
4-Methyl-10H-indolo[3,2-b]thieno[2,3-d]pyridine (22): white crystals, mp 238-240 ˚C; 1H NMR (CD3COCD3) δ 11.99 (s, br, 1H), 8.17 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 5.1 Hz, 1H), 7.80 (d, J = 5.4 Hz, 1H), 7.58 (d, J = 4.08, 1H), 7.45 (t, J = 7.32, 1H), 7.26 (t, J = 7.32, 1H), 2.96 (s, 3H); 13C NMR (CD3COCD3) δ 153.8, 134.8, 128.6, 128.2, 126.2, 126.0, 125.1, 124.3, 124.1, 120.1, 120.1, 111.8, 110.0, 22.3; HRMS (ESI) m/z calcd for C14H11N2S (MH+) 239.0643, found 239.0649.
4-Phenyl-10H-indolo[3,2-b]thieno[2,3-d]pyridine (23): light orange crystals, 229-231˚C; 1H NMR (CD3COCD3) δ 11.95 (s, br, 1H), 8.34 (d, J =7.6, 1H), 7.98 (m, 2H), 7.83 (d, J = 5.5 Hz, 1H), 7.78 (d, J = 5.5 Hz, 1H), 7.67 (d, J = 8.4, 1H), 7.60 (t, J = 8.2, 2H), 7.51 (t, J = 8.2, 2H), 7.33 (t, J = 7.0 Hz, 1H); 13C NMR (CD3COCD3) δ 148.3, 141.5, 140.3, 132.8, 131.6 129.6, 128.5, 128.1, 127.7, 126.7, 125.8, 125.1, 123.6, 120.4, 120.4, 114.3, 112.0; HRMS (ESI) m/z calcd for C19H13N2S (MH+) 301.0799, found 301.0790.