HETEROCYCLES

Paper | Special issue | Vol. 80, No. 2, 2010, pp. 1027-1045
Received, 27th July, 2009, Accepted, 4th September, 2009, Published online, 8th September, 2009.
DOI: 10.3987/COM-09-S(S)79

■ Synthetic Study Directed toward Derivatives of Biologically Active Indolo[2,3-a]carbazole

Masako Sato, Yoshiaki Suzuki, Fumio Yamada, and Masanori Somei*

Faculty of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Various derivatives of (6R*,6aR*)-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8) and 6-cyano-5-hydroxyindolo[2,3-a]carbazole (9) are prepared. Preparations of (6R*,6aR*,11aR*)-6-chloro-11a-cyano-6a-hydroxy- (11) and 12-substituted 6-(Z)-aminomethylidene-5,6,6a,11,11a,12-hexahydroindolo[2,3-a]carbazole-5-ones (15) are also reported.

We have proposed a new concept for evaluating originality and efficiency of synthetic method introducing three measures such as originality rate, intellectual property factor, and application potential factor and defined an ideal synthetic method.2 In our continuing research, we have created a synthetic method,3 as one of the concrete example of the ideal synthesis, for 6-cyano-5-methoxy-12- methylindolo[2,3-a]carbazole (1, Scheme 1) isolated from blue-green alga Nostoc sphaericum (strain EX-5-1) by Moore and co-workers.4 The synthesis starts from indigo (2) and consists of six steps. Every compound involved in the synthesis has either a useful function or a biological activity. Thus, starting material is a widely used dye5 and the target 1 is a cytotoxic and antiviral alkaloid.4 The compound 3 exhibits potent biological activity against telomerase.6 In addition, we have discovered as intellectual properties that 4, 6, and 7 are potent inhibitors of blood platelet aggregation7 while 5 is a promising a2-blocker.8
It is natural, therefore, that we would expect to discover a compound becoming medicine in the future among derivatives of biologically active 5 and 7. Now, we wish to report the synthesis of various derivatives of 5 and 7. Interesting formations of (6R*,6aR*,11aR*)-6-chloro-11a-cyano-6a-hydroxy-5,6,6a,11,11a,12-hexahydro- (11) and 12-substituted (Z)-6-aminomethylidene-5,6,11,12- tetrahydroindolo[2,3-a]carbazole-5-one (15) are also reported.

First, the compound 5 was prepared according to our procedures3 from indigo in three steps in 73% overall yield. Subsequent treatment of 5 in N,N-dimethylformamide (DMF) in the presence of K2CO3 with n-butyl iodide, allyl bromide, propargyl bromide, benzyl bromide, phenethyl bromide, and (E)-cinnamyl bromide provided 8a, 8b, 8c, 8d, 8e, and 8f in the respective yields of 71, 96, 50, 78, 57, and 96% (Scheme 2). Similar treatment of 5 with reagents having a cyano or a carbonyl group such as chloroacetonitrile, N,N-dimethyl-2-chloroacetamide, methyl bromoacetate, methyl acrylate, and phenacyl bromide afforded 8g, 8h, 8i, 8j, and 8k in the respective yields of 62, 90, 72, 26, and 97%. Although the reaction of 1,3-dibromopropane with 5 similarly proceeded to give 8l in 45% yield, ethyl 4-bromobutylate did not react with 5 at all. To overcome the problem, change of the base from K2CO3 to NaH in anhydrous DMF was successful to obtain the desired 8m in 59% yield.
In the reaction of 5 with an E,Z mixture of 1,3-dichloropropene, NaH in anhydrous DMF was the reaction conditions of choice, providing 12-(Z)- 8n and 12-(E)-(3-chloroallyl) derivatives 8o in 42 and 24% yields, respectively. Under similar reaction conditions, 5 reacted with acetyl chloride to produce 12-acetyl compound 8p in 41% yield.
With various 12-substituted (6R*,6aR*)-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]- carbazole-5-one in hand, we next employed our reductive cyanation which realized transformation of 6 to 7. Thus, the treatment of 8a with NaCN in DMF-H2O provided 12-n-butyl-6-cyano-5- hydroxyindolo[2,3-a]carbazole (9a) in 85% yield. A possible reaction mechanism is shown in Scheme 3. The initial step would be a nucleophilic substitution for 6b-chloride by cyanide from the back side to give A. After dehydration, the resultant B can form C by general acid promoted cyanide addition to the 6-position. Subsequent cyanide attack at one of the geminal cyano groups of C achieves the reductive cyanation with the liberation of dicyan and an enolate of 9a. The other possible route is the enolization of 5-carbonyl of A, followed by the addition of cyanide at the imine carbon (C11a) from the less sterically hindered a-side culminating in the formation of D. Subsequent cyanide attack at the 11a-cyano group and concomitant general acid promoted elimination of 6ab-hydroxy group liberates dicyan and 9a.

On the basis of above results, the reductive cyanation was applied to 8b—h and 8m resulting in the formations of 9b, 9c, 9d, 9e, 9f, 9g, 9h, and 9m in the respective yields of 91, 72, 98, 85, 80, 54, 95, and 72%. In the case of 8i, the reductive cyanation formed 9i and 9q in 17 and 43% yields, respectively. Similar reaction of 8k removed the 12-phenacyl group to afford 10 in 27% yield together with 16% yield of starting material.
The structures of 9a—i and 9m,q were established unequivocally by pursuing X-ray single-crystal analysis of 9a as a representative of them and the results are shown in Figure 1 and Table 1. It is interesting to note that this type of compounds 9 tends to involve a recrystallization solvent molecule in crystals. In fact, the ORTEP drawing of 9a demonstrates EtOAc molecule.

The reaction of 8l with NaCN in DMF-H2O provided 9l and 9r in 23 and 23% yields, respectively. The reaction of about 4:1 mixture of 8n and 8o produced 9n and 9o in 41 and 14% yields, respectively. It is interesting to note that the similar reaction of 8p afforded 10 and the unexpected (6R*,6aR*,11aR*)-6-
chloro-11a-cyano-6a-hydroxy-5,6,6a,11,11a,12-hexahydroindolo[2,3-a]carbazole-5-one (11) in 22 and 74% yields, respectively, though formation of the desired 9p was not observed at all.
Reduction of 11 with NaBH4 proceeded slowly from the less hindered β-side to provide 5α-hydroxy compound 12a in 47% yield. Further treatment of 12a with acetic anhydride gave 5α-acetoxy compound 12b in 30% yield. Comparing 1H-NMR spectra of 12a and 12b, the coupling constant between H5 and H6 is shown to be 8.2 Hz, which proved their stereochemistries as shown in the Scheme 2.
It should be noted that the absorption bands of cyano group of 11, 12a, and 12b were very weak or almost invisible in their infrared spectra. Therefore, X-ray single-crystal analysis of 11 was necessary for the determination of the structure. The results shown in Figure 2 and Table 2 demonstrate both the presence of the cyano group at the 11a-position and the stereochemistries of 6, 6a, and 11a positions being all R*.
Methylation of 9d with ethereal diazomethane smoothly proceeded to afford the corresponding methoxy compound 13 in 82% yield. All attempts to hydrolyze the 6-cyano group of 13 to 6-carboxy or 6-carbamoyl group with base were unsuccessful. Under severe conditions such as treatment of 13 with solid NaOH in refluxing ethylene glycol resulted in the methyl ether cleavage to afford 9d in 62% yield.
Further attempt to obtain 6-formyl type compound 14 by the reaction of 9 with diisobutyl aluminum hydride (DIBAL) proceeded in an unexpected way. Thus the reduction of 9a and 9d with DIBAL afforded 15a and 15b in 73 and 47% yields, respectively. In the 1H-NMR spectrum of 15a, hydrogen bonded Ha was observed at lower δ 12.0 (1H, dd, J=13.8, 8.2 Hz), while Hb and Hc protons appeared at δ 8.60 (1H, brt, J=8.2 Hz) and 8.84 (1H, dd, J=13.8, 8.2 Hz), respectively. On the addition of D2O, both Ha and Hb protons disappeared and Hc collapsed to a singlet. Similar phenomena were observed in case of 15b. Further treatment of 15a with Ac2O afforded N-acetyl compound 16 in 87% yield. These results prove the 6-aminomethylidene structures of 15a,b.
A possible reaction mechanism for the transformation of 9 to 15 is shown in Scheme 4. The initial reaction of DIBAL with 9 forms aluminum complex A, followed by the intramolecular reduction of cyano group with hydride to afford B. Hydrolysis of B affords an enol form compound C which tautomerizes to a carbonyl form product 15 forming a stable enamide system.

In summary, we succeeded in preparing various derivatives of 8 and 9, together with new classes of compound, 11 and 15. Biological evaluations of new compounds in this report are in progress.

EXPERIMENTAL
Melting points were determined on a Yanagimoto micro melting point apparatus and are uncorrected. Infrared (IR) spectra were recorded with a Shimadzu IR-420 or Horiba FT-720 spectrophotometer and proton nuclear magnetic resonance (1H-NMR) spectra with a JEOL GSX-500 spectrometer with tetramethylsilane as an internal standard. Mass spectra (MS) were recorded on a JEOL JMS-SX102A instruments. Column chromatography was performed on silica gel (SiO2, 100—200 mesh, from Kanto Chemical Co., Inc.) throughout the present study.
(6R*,6aR*)-12-n-Butyl-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8a) from (6R*,6aR*)-6-Chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (5) — General Procedure A: K2CO3 (72.1 mg, 0.52 mmol) and n-butyl iodide (0.34 mL, 2.90 mmol) were added to a solution of 5 (48.1 mg, 0.15 mmol) in DMF (3.0 mL), and the mixture was stirred for 20 min at rt. After addition of H2O under ice cooling, the whole was extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with EtOAc–hexane (1:5, v/v) to give 8a (40.1 mg, 71%). 8a: mp 187—189˚C (decomp., orange prisms, recrystallized from CHCl3). IR (KBr): 3421, 1653, 1479, 1346, 1086, 754 cm-1. 1H-NMR (CDCl3) δ: 0.97 (3H, t, J=7.4 Hz), 1.39—1.50 (2H, m), 1.87—2.00 (2H, m), 3.11 (1H, s, disappeared on addition of D2O), 4.63 (1H, ddd, J=14.1, 8.2, 6.4 Hz), 4.76 (1H, s), 4.87 (1H, ddd, J=14.1, 8.2, 6.4 Hz), 7.35 (1H, td, J=7.7, 1.2 Hz), 7.39 (1H, td, J=7.7, 1.2 Hz), 7.47 (1H, td, J=7.7, 1.2 Hz), 7.50 (1H, d, J=7.7 Hz), 7.50 (1H, td, J=7.7, 1.2 Hz), 7.72 (1H, d, J=7.7 Hz), 7.92 (1H, d, J=7.7 Hz), 8.39 (1H, d, J=7.7 Hz). MS m/z: 380 and 378 (M+). Anal. Calcd for C22H19N2O2Cl·1/8H2O: C, 69.33; H, 5.09; N, 7.35. Found: C, 69.38; H, 5.11; N, 7.24.
(6R*,6aR*)-12-Allyl-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8b) from 5 — In the general procedure A, K2CO3 (754 mg, 5.44 mmol), allyl bromide (2.70 mL, 31.1 mmol), 5 (501 mg, 1.56 mmol), and DMF (10.0 mL) were used. The reaction time was 30 min. After column-chromatography, 8b (540 mg, 96%) was obtained. 8b: mp 202—203˚C (decomp., yellow prisms, recrystallized from EtOAc). IR (KBr): 3400, 3110, 1665, 1562, 1457, 1333, 1140, 1087, 1017, 789, 747 cm-1. 1H-NMR (DMSO-d6) δ: 5.16 (1H, dd, J=17.1, 1.5 Hz), 5.22 (1H, dd, J=10.3, 1.5 Hz), 5.35 (1H, s), 5.36 (1H, dd, J=16.3, 5.4 Hz), 5.53 (1H, dd, J=16.3, 5.4 Hz), 6.07—6.16 (1H, m), 6.84 (1H, s), 7.39 (1H, t, J=8.1 Hz), 7.40 (1H, t, J=8.1 Hz), 7.50 (1H, t, J=7.5 Hz), 7.55 (1H, t, J=7.5 Hz), 7.75 (1H, d, J=8.1 Hz), 7.77 (1H, d, J=7.5 Hz), 7.84 (1H, d, J=7.5 Hz), 8.19 (1H, d, J=8.1 Hz). MS m/z: 364 and 362 (M+). Anal. Calcd for C21H15N2O2Cl: C, 69.52; H, 4.17; N, 7.72. Found: C, 69.49; H, 4.17; N, 7.41.
(6R*,6aR*)-6-Chloro-6a-hydroxy-12-propargyl-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8c) from 5 — In the general procedure A, K2CO3 (44.2 mg, 0.32 mmol), propargyl bromide (0.14 mL, 1.83 mmol), 5 (29.5 mg, 0.09 mmol), and DMF (2.0 mL) were used. The reaction time was 1 h. After column-chromatography, 8c (16.5 mg, 50%) was obtained. 8c: mp 248˚C (decomp., dark yellow powder, recrystallized from EtOAc–hexane). IR (KBr): 3359, 3286, 1653, 1475, 1086, 791, 746 cm-1. 1H-NMR (DMSO-d6) δ: 3.48 (1H, t, J=2.5 Hz), 5.38 (1H, d, J=1.5 Hz, collapsed to s on addition of D2O), 5.66 (1H, dd, J=17.9, 2.5 Hz), 5.78 (1H, dd, J=17.9, 2.5 Hz), 6.91 (1H, d, J=1.5 Hz, disappeared on addition of D2O), 7.41 (1H, td, J=7.7, 1.3 Hz), 7.45 (1H, td, J=7.7, 1.3 Hz), 7.56 (1H, td, J=7.7, 1.3 Hz), 7.56 (1H, td, J=7.7, 1.3 Hz), 7.81 (1H, d, J=7.7 Hz), 7.84 (1H, d, J=7.7 Hz), 7.84 (1H, d, J=7.7 Hz), 8.19 (1H, d, J=7.7 Hz). MS m/z: 362 and 360 (M+). Anal. Calcd for C21H13N2O2Cl·1/2H2O: C, 68.21; H, 3.82; N, 7.58. Found: C, 68.00; H, 3.73; N, 7.33.
(6R*,6aR*)-12-Benzyl-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8d) from 5 — In the general procedure A, K2CO3 (619 mg, 4.48 mmol), benzyl bromide (3.10 mL, 25.6 mmol), 5 (413 mg, 1.28 mmol), and DMF (8.0 mL) were used. The reaction time was 75 min. After column-chromatography, 8d (411 mg, 78%) was obtained. 8d: mp 219.5—221.5 ˚C (yellow prisms, recrystallized from EtOAc–hexane). IR (KBr): 3356, 1685, 1577, 1473, 1142, 771 cm-1. 1H-NMR (DMSO-d6) δ: 5.41 (1H, s), 5.99 (1H, d, J=15.8 Hz), 6.18 (1H, d, J=15.8 Hz), 6.91 (1H, br s, disappeared on addition of D2O), 7.26 (1H, t, J=7.2 Hz), 7.30 (2H, t, J=7.2 Hz), 7.37 (2H, d, J=7.2 Hz), 7.40 (1H, td, J=7.4, 1.2 Hz), 7.42 (1H, td, J=7.4, 1.2 Hz), 7.42 (1H, td, J=7.4, 1.2 Hz), 7.54 (1H, td, J=7.4, 1.2 Hz), 7.64 (1H, d, J=7.4 Hz), 7.75 (1H, d, J=7.4 Hz), 7.86 (1H, d, J=7.4 Hz), 8.19 (1H, d, J=7.4 Hz). MS m/z: 414 and 412 (M+). Anal. Calcd for C25H17N2O2Cl·1/2H2O: C, 71.17; H, 4.30; N, 6.64. Found: C, 71.32; H, 4.25; N, 6.49.
(6R*,6aR*)-6-Chloro-6a-hydroxy-12-phenethyl-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8e) from 5 — In the general procedure A, K2CO3 (45.0 mg, 0.33 mmol), phenethyl bromide (0.25 mL, 1.86 mmol), 5 (30.0 mg, 0.09 mmol), and DMF (2.0 mL) were used. The reaction time was 1 h. After column-chromatography, 8e (22.6 mg, 57%) was obtained. 8e: mp 183—184 ˚C (yellow needles, recrystallized from EtOAc–hexane). IR (KBr): 3361, 1655, 1477, 1146, 746 cm-1. 1H-NMR (DMSO-d6) δ: 3.19 (2H, td, J=13.8, 6.8 Hz), 4.83 (1H, ddd, J=13.8, 8.6, 6.8 Hz ), 5.04 (1H, ddd, J=13.8, 8.6, 6.8 Hz), 5.36 (1H,s), 6.84 (1H, br s, disappeared on addition of D2O), 7.21 (1H, br t, J=7.4 Hz), 7.30 (2H, t, J=7.4 Hz), 7.35 (2H, d, J=7.4 Hz), 7.37 (1H, t, J=7.5 Hz), 7.41 (1H, t, J=7.5 Hz), 7.43 (1H, t, J=7.5 Hz), 7.58 (1H, t, J=7.5 Hz), 7.73 (1H, d, J=7.5 Hz), 7.84 (1H, d, J=7.5 Hz), 7.86 (1H, d, J=7.5 Hz), 8.15 (1H, d, J=7.5 Hz). MS m/z: 428 and 426 (M+). Anal. Calcd for C26H19N2O2Cl·1/2H2O: C, 71.64; H, 4.62; N, 6.43. Found: C, 71.86; H, 4.43; N, 6.40.
(6R*,6aR*)-6-Chloro-12-(E)-cinnamyl-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5- one (8f) from 5 — In the general procedure A, K2CO3 (157 mg, 1.14 mmol), cinnamyl bromide (0.79 mL, 6.49 mmol), 5 (105 mg, 0.32 mmol), and DMF (6.0 mL) were used. The reaction time was 1 h. After column-chromatography, 8f (137 mg, 96%) was obtained. 8f: mp 205—208˚C (brown plates, recrystallized from EtOAc—hexane). IR (KBr): 3390, 1648, 1579, 1473, 1145, 757 cm-1. 1H-NMR (DMSO-d6) δ: 5.36 (1H, d, J=1.5 Hz, collapsed to s on addition of D2O), 5.51 (1H, ddd, J=16.5, 5.9, 1.2 Hz), 5.71 (1H, ddd, J=16.5, 5.9, 1.2 Hz), 6.53 (1H, dt, J=16.5, 5.9 Hz), 6.69 (1H, d, J=16.5 Hz), 6.85 (1H, d, J=1.5 Hz, disappeared on addition of D2O), 7.22 (1H, t, J=7.4 Hz), 7.28 (2H, t, J=7.4 Hz), 7.37 (2H, d, J=7.4 Hz), 7.40 (1H, td, J=7.6, 1.2 Hz), 7.41 (1H, td, J=7.6, 1.2 Hz), 7.50 (1H, td, J=7.6, 1.2 Hz), 7.55 (1H, td, J=7.6, 1.2 Hz), 7.80 (1H, d, J=7.6 Hz), 7.85 (1H, d, J=7.6 Hz), 7.85 (1H, d, J=7.6 Hz), 8.20 (1H, d, J=7.6 Hz). MS m/z: 440 and 438 (M+). Anal. Calcd for C27H19N2O2Cl·1/2EtOAc: C, 72.12; H, 4.80; N, 5.80. Found: C, 71.84; H, 4.68; N, 5.83.
(6R*,6aR*)-6-Chloro-12-cyanomethyl-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8g) from 5 — In the general procedure A, K2CO3 (159 mg, 1.15 mmol), chloroacetonitrile (0.42 mL, 6.56 mmol), 5 (106 mg, 0.33 mmol), and DMF (3.0 mL) were used. The reaction time was 15 min. After column-chromatography, 8g (72.6 mg, 62%) was obtained. 8g: mp 249.5—251.5˚C (decomp., yellow prisms, recrystallized from EtOAc). IR (KBr): 3350, 1648, 1615, 1574, 1472, 1345, 1083, 797, 780, 747 cm-1. 1H-NMR (DMSO-d6) δ: 5.41 (1H, d, J=1.5 Hz, collapsed on addition of D2O), 5.99 (1H, d, J=18.1 Hz), 6.10 (1H, d, J=18.1 Hz), 6.95 (1H, d, J=1.5 Hz, disappeared on addition of D2O), 7.42 (1H, td, J=7.6, 1.1 Hz), 7.49 (1H, td, J=7.6, 1.1 Hz), 7.57 (1H, td, J=7.6, 1.1 Hz), 7.62 (1H, td, J=7.6, 1.1 Hz), 7.82 (1H, d, J=7.6 Hz), 7.85 (1H, d, J=7.6 Hz), 7.95 (1H, d, J=7.6 Hz), 8.21 (1H, d, J=7.6 Hz). Anal. Calcd for C20H12N3O2Cl: C, 66.40; H, 3.34; N, 11.61. Found: C, 66.70; H, 3.33; N, 11.37.
(6R*,6aR*)-6-Chloro-12-N,N-dimethylcarbamoylmethyl-6a-hydroxy-5,6,6a,12-tetrahydroin-dolo- [2,3-a]carbazole-5-one (8h) from 5 — In the general procedure A, K2CO3 (89.2 mg, 0.65 mmol), N,N-dimethyl-2-chloroacetamide (0.66 mL, 6.46 mmol), 5 (104 mg, 0.32 mmol), and DMF (6.0 mL) were used. The reaction time was 1.5 h. After column-chromatography, 8h (118 mg, 90%) was obtained. 8h: mp 257—258˚C (decomp., dark brown prisms, recrystallized from MeOH). IR (KBr): 3410, 1670, 1647, 1583, 1481, 775, 756 cm-1. 1H-NMR (DMSO-d6) δ: 2.90 (3H, s), 3.24 (3H, s), 5.31 (1H, s), 5.64 (1H, d, J=16.8 Hz), 5.81 (1H, d, J=16.8 Hz), 6.83 (1H, s, disappeared on addition of D2O), 7.37 (1H, td, J=7.5, 1.2 Hz), 7.39 (1H, td, J=7.5, 1.2 Hz), 7.47 (1H, td, J=7.5, 1.2 Hz), 7.52 (1H, td, J=7.5, 1.2 Hz), 7.66 (1H, d, J=7.5 Hz), 7.72 (1H, d, J=7.5 Hz), 7.82 (1H, d, J=7.5 Hz), 8.17 (1H, d, J=7.5 Hz). MS m/z: 409 and 407 (M+). Anal. Calcd for C22H18N3O3Cl·1/4H2O: C, 64.08; H, 4.52; N, 10.19. Found: C, 64.21; H, 4.52; N, 10.00.
(6R*,6aR*)-6-Chloro-6a-hydroxy-12-methoxycarbonylmethyl-5,6,6a,12-tetrahydroindolo[2,3-a]- carbazole-5-one (8i) from 5 — In the general procedure A, K2CO3 (68.2 mg, 0.48 mmol), methyl bromoacetate (0.16 mL, 1.61 mmol), 5 (51.8 mg, 0.16 mmol), and DMF (2.0 mL) were used. The reaction time was 30 min. After column-chromatography, 8i (45.8 mg, 72%) was obtained. 8i: mp 223—224.5˚C (decomp., brown prisms, recrystallized from EtOAc). IR (KBr): 3415, 1749, 1655, 1479, 1342, 1086, 1012, 800, 777, 756 cm-1. 1H-NMR (DMSO-d6) δ: 3.74 (3H, s), 5.36 (1H, s), 5.58 (1H, d, J=18.0 Hz), 5.81 (1H, d, J=18.0 Hz), 6.84 (1H, s, disappeared on addition of D2O), 7.39 (1H, t, J=7.8 Hz), 7.42 (1H, t, J=7.8 Hz), 7.48—7.56 (2H, m), 7.73 (1H, d, J=7.8 Hz), 7.79 (1H, d, J=7.8 Hz), 7.82 (1H, d, J=7.8 Hz), 8.18 (1H, d, J=7.8 Hz). Anal. Calcd for C21H15N2O4Cl: C, 63.89; H, 3.83; N, 7.10. Found: C, 63.65; H, 3.84; N, 6.89.
(6R*,6aR*)-6-Chloro-6a-hydroxy-12-[2-(methoxycarbonyl)ethyl]-5,6,6a,12-tetrahydroindolo[2,3-a]-carbazole-5-one (8j) from 5 — In the general procedure A, K2CO3 (68.7 mg, 0.47 mmol), methyl acrylate (0.29 mL, 3.16 mmol), 5 (50.8 mg, 0.16 mmol), and DMF (3.0 mL) were used. The reaction time was 30 min. After column-chromatography, 8j (17.0 mg, 26%) and the unreacted 5 (18.5 mg, 36%) were obtained in the order of elution. 8j: mp 216.5—218˚C (decomp., yellow powder, recrystallized from EtOAc). IR (KBr): 3431, 1714, 1680, 1583, 1479, 1439, 1215, 1146, 773, 754 cm-1. 1H-NMR (DMSO-d6) δ: 3.02 (2H, t, J=7.2 Hz), 3.58 (3H, s), 4.86 (1H, dt, J=14.2, 7.2 Hz), 5.14 (1H, dt, J=14.2, 7.2 Hz), 5.33 (1H, d, J=1.5, collapsed on addition of D2O), 6.79 (1H, d, J=1.5, disappeared on addition of D2O), 7.39 (1H, td, J=7.7, 1.2 Hz), 7.40 (1H, td, J=7.7, 1.2 Hz), 7.51 (1H, td, J=7.7, 1.2 Hz), 7.55 (1H, td, J=7.7, 1.2 Hz), 7.77 (1H, d, J=7.7 Hz), 7.83 (1H, d, J=7.7 Hz), 7.87 (1H, d, J=7.7 Hz), 8.17 (1H, d, J=7.7 Hz). Anal. Calcd for C22H17N2O4Cl: C, 64.59; H, 4.19; N, 6.66. Found: C, 64.63; H, 4.19; N, 6.85.
(6R*,6aR*)-6-Chloro-6a-hydroxy-12-phenacyl-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8k) from 5 — In the general procedure A, K2CO3 (172 mg, 1.25 mmol), phenacyl bromide (1.42 g, 7.10 mmol), 5 (115 mg, 0.33 mmol), and DMF (6.0 mL) were used. The reaction time was 1.5 h. After column-chromatography, 8k (152 mg, 97%) was obtained. 8k: mp 217—219˚C (yellow plates, recrystallized from EtOAc—hexane). IR (KBr): 3372, 1697, 1579, 1475, 1230, 752 cm-1. 1H-NMR (DMSO-d6) δ: 5.36 (1H, d, J=1.4 Hz, collapsed to s on addition of D2O), 6.38 (1H, d, J=18.3 Hz), 6.52 (1H, d, J=18.3 Hz), 6.84 (1H, d, J=1.4 Hz, disappeared on addition of D2O), 7.34 (1H, td, J=7.6, 1.3 Hz), 7.42 (1H, td, J=7.6, 1.3 Hz), 7.45 (1H, td, J=7.6, 1.3 Hz), 7.47 (1H, td J=7.6, 1.3 Hz), 7.51 (1H, d, J=8.3 Hz), 7.67 (2H, t, J=8.3 Hz), 7.76 (1H, d, J=7.6 Hz), 7.77 (1H, t, J=8.3 Hz), 7.80 (1H, d, J=7.6 Hz), 8.17 (1H, d, J=7.6 Hz), 8.18 (1H, d, J=7.6 Hz), 8.21 (1H, d, J=7.6 Hz). MS m/z: 442 and 440 (M+). Anal. Calcd for C26H17N2O3Cl: C, 70.83; H, 3.89; N, 6.35. Found: C, 70.67; H, 3.91; N, 6.24.
(6R*,6aR*)-12-(3-Bromopropyl)-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole- 5-one (8l) from 5 — In the general procedure A, K2CO3 (45.7 mg, 0.33 mmol), 1,3-dibromopropane (0.19 mL, 1.89 mmol), 5 (30.5 mg, 0.09 mmol), and DMF (2.0 mL) were used. The reaction time was 50 min. After column-chromatography, 8l (18.9 mg, 45%) was obtained. 8l: mp 148—150˚C (orange plates, recrystallized from CHCl3). IR (KBr): 3400, 1651, 1581, 1479, 1080, 758 cm-1. 1H-NMR (CDCl3) δ: 2.51—2.63 (2H, m), 3.12 (1H, br s, disappeared on addition of D2O), 3.46 (1H, ddd, J=10.4, 6.9, 5.7 Hz), 3.52 (1H, ddd, J=10.4, 6.9, 5.7 Hz), 4.76 (1H, s), 4.80 (1H, ddd, J=14.2, 7.6, 6.5 Hz), 5.02 (1H, dt, J=14.4, 7.1 Hz), 7.36 (1H, td, J=7.8, 1.1 Hz), 7.41 (1H, td, J=7.8, 1.1 Hz), 7.50 (1H, td, J=7.8, 1.1 Hz), 7.52 (1H, td, J=7.8, 1.1 Hz), 7.62 (1H, d, J=7.8 Hz), 7.73 (1H, d, J=7.8 Hz), 7.92 (1H, d, J=7.8 Hz), 8.39 (1H, d, J=7.8 Hz). HR-MS (FAB+): Calcd for C21H16N2O281Br37Cl: 447.0112. Found: 447.0084. C21H16N2O279Br37Cl: 445.0132. Found: 445.0109. C21H16N2O281Br35Cl: 445.0141. Found: 445.0109. C21H16N2O279Br35Cl: 443.0162. Found: 443.0132. Anal. Calcd for C21H16N2O2BrCl·1/4H2O: C, 56.27; H, 3.71; N, 6.25. Found: C, 56.33; H, 3.65; N, 5.95.
(6R*,6aR*)-6-Chloro-12-[3-(ethoxycarbonyl)propyl]-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]- carbazole-5-one (8m) from 5 — General Procedure B: A solution of 5 (28.9 mg, 0.09 mmol) in anhydrous DMF (2.0 mL) was added to 60% NaH (3.7 mg, 0.09 mmol) at 0°C with stirring under argon atmosphere. After additional stirring at rt, ethyl 4-bromobutylate (0.26 mL, 1.79 mmol) was added and the mixture was stirred fot 1 h at rt. After addition of EtOAc, the whole was washed successively with H2O, brine, and dried over Na2SO4, then evaporated under reduced pressure to leave an oil, which was column-chromatographed repeatedly on SiO2 with EtOAc–hexane (1:2, v/v) to give 8m (23.2 mg, 59%) and unreacted 5 (2.80 mg, 10%) in the order of elution. 8m: (brown viscous oil). IR (film): 3367, 1707, 1672, 1579, 1481, 1200, 750 cm-1. 1H-NMR (CDCl3) δ: 1.15 (3H, t, J=7.1 Hz), 2.17 (2H, q, J=7.1 Hz), 2.38— 2.43 (2H, m), 4.04 (2H, q, J=7.1 Hz), 4.70 (1H, dt, J=14.2, 7.1 Hz), 4.91 (1H, dt, J=14.2, 7.1 Hz), 5.32 (1H, d, J=1.3 Hz, collapsed to s on addition of D2O), 6.82 (1H, d, J=1.3 Hz, disappeared on addition of D2O), 7.39 (1H, t, J=7.8 Hz), 7.41 (1H, t, J=7.8 Hz), 7.52 (1H, td, J=7.8, 1.2 Hz), 7.55 (1H, td, J=7.8, 1.2 Hz), 7.76 (1H, d, J=7.8 Hz), 7.84 (1H, d, J=7.8 Hz), 7.84 (1H, d, J=7.8 Hz), 8.19 (1H, d, J=7.8 Hz). HR-MS m/z: Calcd for C24H21N2O437Cl: 438.1160. Found: 438.1140. C24H21N2O435Cl: 436.1189. Found: 436.1184.
(6R*,6aR*)-6-Chloro-12-[(Z)-3-chloroallyl]- (8n) and -12-[(E)-3-chloroallyl]-6a-hydroxy-5,6,6a,12- tetrahydroindolo[2,3-a]carbazole-5-one (8o) from 5 — In the general procedure B, 5 (63.5 mg, 0.20 mmol), anhydrous DMF (4.0 mL), 60% NaH (7.90 mg, 0.20 mmol), and (E,Z) mixture of 1,3-dichloropropene (0.36 mL, 3.94 mmol) were used. After repeated column-chromatography, 8n (32.9 mg, 42%), 8o (18.4 mg, 24%), and unreacted 5 (9.10 mg, 14%) were obtained in the order of elution. 8n: mp 207—209˚C (decomp., yellow powder, recrystallized from EtOAc). IR (KBr): 3381, 1649, 1616, 1581, 1475, 802, 754, 739 cm-1. 1H-NMR (DMSO-d6) δ: 5.34 (1H, s), 5.48 (1H, ddd, J=16.1, 6.5, 2.3 Hz), 5.73 (1H, ddd, J=16.1, 6.5, 2.3 Hz), 6.17 (1H, q, J=6.5 Hz), 6.63 (1H, dt, J=6.5, 2.3 Hz), 6.84 (1H, br s, disappeared on addition of D2O), 7.40 (1H, td, J=7.6, 1.1 Hz), 7.43 (1H, td, J=7.6, 1.1 Hz), 7.53 (1H, td, J=7.6, 1.1 Hz), 7.55 (1H, td, J=7.6, 1.1 Hz), 7.68 (1H, d, J=7.6 Hz), 7.78 (1H, d, J=7.6 Hz), 7.84 (1H, d, J=7.6 Hz), 8.19 (1H, d, J=7.6 Hz). MS m/z: 400, 398, and 396 (M+). Anal. Calcd for C21H14N2O2Cl2·1/4H2O: C, 62.78; H, 3.64; N, 6.97. Found: C, 63.00; H, 3.58; N, 6.95. 8o: brown oil. IR (film): 3417, 1653, 1577, 1471, 1146, 748 cm-1. 1H-NMR (DMSO-d6) δ: 5.34 (1H, d, J=1.5 Hz, collapsed to s on addition of D2O), 5.36 (1H, ddd, J=13.4, 6.8, 1.7 Hz), 5.53 (1H, ddd, J=13.4, 6.8, 1.7 Hz), 6.30 (1H, dt, J=13.4, 6.8 Hz), 6.74 (1H, d, J=13.4 Hz), 6.81 (1H, d, J=1.5 Hz, disappeared on addition of D2O), 7.40 (1H, td, J=7.6, 1.1 Hz), 7.42 (1H, t, J=7.6 Hz), 7.52 (1H, td, J=7.6, 1.1 Hz), 7.55 (1H, td, J=7.6, 1.1 Hz), 7.80 (1H, d, J=7.6 Hz), 7.84 (1H, d, J=7.6 Hz), 7.87 (1H, d, J=7.6 Hz), 8.18 (1H, d, J=7.6 Hz). HR-MS m/z: Calcd for C21H14N2O237Cl2: 400.0374. Found: 400.0339. C21H14N2O237Cl35Cl: 398.0403. Found: 398.0406. C21H14N2O235Cl2: 396.0433. Found: 396.0449.
(6R*,6aR*)-12-Acetyl-6-chloro-6a-hydroxy-5,6,6a,12-tetrahydroindolo[2,3-a]carbazole-5-one (8p) from 5 — In the general procedure B, 5 (47.4 mg, 0.15 mmol), anhydrous DMF (2.0 mL), 60% NaH (5.80 mg, 0.15 mmol), and acetyl chloride (0.21 ml, 2.94 mmol) were used. After repeated column-chromatography, 8p (22.2 mg, 41%) and unreacted 5 (10.9 mg, 23%) were obtained in the order of elution. 8p: mp 209—211˚C (decomp., yellow fine needles, recrystallized from EtOAc). IR (KBr): 3332, 1695, 1685, 1571, 1284, 1263, 760 cm-1. 1H-NMR (DMSO-d6) δ: 2.92 (3H, s), 5.31 (1H, s), 7.08 (1H, br s, disappeared on addition of D2O), 7.44 (1H, td, J=7.9, 1.3 Hz ), 7.52 (1H, t, J=7.9 Hz), 7.58 (1H, td, J=7.9, 1.3 Hz), 7.61 (1H, td, J=7.9 Hz), 7.80 (1H, d, J=7.9 Hz), 7.83 (1H, d, J=7.9 Hz), 8.22 (2H, d, J=7.9 Hz). MS m/z: 366 and 364 (M+). Anal. Calcd for C20H13N2O3Cl·EtOAc: C, 63.65; H, 4.67; N, 6.19. Found: C, 63.42; H, 4.53; N, 6.37.
12-n-Butyl-6-cyano-5-hydroxyindolo[2,3-a]carbazole (9a) from 8a — General Procedure C: NaCN (239 mg, 5.72 mmol) was added to a solution of 8a (61.5 mg, 0.16 mmol) in DMF (4.0 mL) and H2O (2.0 mL), and the mixture was stirred for 0.5 h at rt. After addition of H2O, the whole was extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with EtOAc–hexane (1:3, v/v) to give 9a (48.9 mg, 85%). 9a: mp 251—253˚C (pale gray powder, recrystallized from EtOAc). IR (KBr): 3311, 2206, 1705, 1630, 1576, 1414, 737 cm-1. 1H-NMR (DMSO-d6) δ: 0.81 (3H, t, J=7.4 Hz), 1.28 (2H, sex, J=7.4 Hz), 1.82 (2H, quin, J=7.4 Hz), 4.86 (2H, t, J=7.4 Hz), 7.27 (1H, t, J=7.7 Hz), 7.31 (1H, t, J=7.7 Hz), 7.48 (1H, t, J=7.7 Hz), 7.50 (1H, t, J=7.7 Hz), 7.72 (1H, d, J=7.7 Hz), 7.74 (1H, d, J=7.7 Hz), 8.39 (1H, d, J=7.7 Hz), 8.45 (1H, d, J=7.7 Hz), 10.7 (1H, s, disappeared on addition of D2O), 11.5 (1H, s, disappeared on addition of D2O). MS m/z: 353 (M+). Anal. Calcd for C23H19N3O: C, 78.16; H, 5.42; N, 11.89. Found: C, 77.95; H, 5.47; N, 11.69.
12-Allyl-6-cyano-5-hydroxyindolo[2,3-a]carbazole (9b) from 8b — In the general procedure C, NaCN (1.50 g, 28.9 mmol), 8b (349 mg, 0.96 mmol), DMF (18.0 mL), and H2O (9.0 mL) were used. After column-chromatography, 9b (294 mg, 91%) was obtained. 9b: mp 236.5—238˚C (decomp., pale gray cotton fibers, recrystallized from Et2O–hexane). IR (KBr): 3440, 2110, 1625, 1458, 1416, 1354, 1168, 916, 736 cm-1. 1H-NMR (DMSO-d6) δ: 4.75 (1H, d, J=17.4 Hz), 5.06 (1H, d, J=10.5 Hz), 5.49—5.53 (2H, m), 6.10—6.20 (1H, m), 7.26 (1H, t, J=7.6 Hz), 7.33 (1H, t, J=7.6 Hz), 7.47 (1H, t, J=7.6 Hz), 7.49 (1H, t, J=7.6 Hz), 7.69 (2H, d, J=7.6 Hz), 8.39 (1H, d, J=7.6 Hz), 8.44 (1H, d, J=7.6 Hz), 10.73 (1H, br s, disappeared on addition of D2O), 11.53 (1H, s, disappeared on addition of D2O). MS m/z: 337 (M+). Anal. Calcd for C22H15N3O: C, 78.32; H, 4.48; N, 12.46. Found: C, 78.08; H, 4.47; N, 12.29.
6-Cyano-5-hydroxy-12-propargylindolo[2,3-a]carbazole (9c) from 8c — In the general procedure C, NaCN (112 mg, 2.29 mmol), 8c (27.5 mg, 0.08 mmol), DMF (2.0 mL), and H2O (1.0 mL) were used. After column-chromatography, 9c (18.5 mg, 72%) was obtained. 9c: mp 268—270˚C (decomp., pale brown powder, recrystallized from CHCl3). IR (KBr): 3454, 3263, 2206, 1633, 1460, 1242, 742 cm-1. 1H-NMR (DMSO-d6) δ: 3.30—3.31 [1H, m, clearly appeared at 3.23 (1H, t, J=2.2 Hz) on addition of D2O], 5.75 (2H, d, J=2.2 Hz), 7.28 (1H, t, J=7.8 Hz), 7.36 (1H, t, J=7.8 Hz), 7.49 (1H, t, J=7.8 Hz), 7.54 (1H, t, J=7.8 Hz), 7.72 (1H, d, J=7.8 Hz), 7.81 (1H, d, J=7.8 Hz), 8.39 (1H, d, J=7.8 Hz), 8.46 (1H, d, J=7.8 Hz), 10.8 (1H, s, disappeared on addition of D2O), 11.7 (1H, s, disappeared on addition of D2O). MS m/z: 335 (M+). Anal. Calcd for C22H13N3O·1/2H2O: C, 76.73; H, 4.10; N, 12.20. Found: C, 76.86; H, 3.91; N, 11.96.
12-Benzyl-6-Cyano-5-hydroxyindolo[2,3-a]carbazole (9d) from 8d — In the general procedure C, NaCN (123 mg, 3.06 mmol), 8d (32.9 mg, 0.08 mmol), DMF (2.0 mL), and H2O (1.0 mL) were used. After column-chromatography, 9d (30.1 mg, 98%) was obtained. 9d: mp 243—244˚C (decomp., gray needles, recrystallized from EtOAc). IR (KBr): 3282, 2200, 1635, 1576, 1169, 739 cm-1. 1H-NMR (DMSO-d6) δ: 6.13 (2H, s), 7.14—7.25 (5H, m), 7.27 (1H, td, J=7.7, 1.7 Hz), 7.32 (1H, td, J=7.7, 1.7 Hz), 7.43 (1H, td, J=7.7, 1.7 Hz), 7.46 (1H, td, J=7.7, 1.7 Hz), 7.64 (1H, d, J=7.7 Hz), 7.65 (1H, d, J=7.7 Hz), 8.40 (1H, d, J=7.7 Hz), 8.46 (1H, d, J=7.7 Hz), 10.8 (1H, br s, disappeared on addition of D2O), 11.7 (1H, s, disappeared on addition of D2O). MS m/z: 387 (M+). Anal. Calcd for C26H17N3O: C, 80.60; H, 4.42; N, 10.85. Found: C, 80.46; H, 4.47; N, 10.78.
12-Benzyl-6-cyano-5-hydroxyindolo[2,3-a]carbazole (9d) from 13 — Crushed NaOH powder (675 mg, 16.9 mmol) was added to a solution of 13 (9.6 mg, 0.02 mmol) in ethylene glycol (3.0 mL), and the mixture was refluxed for 2 h with stirring. After addition of H2O, the whole was extracted with EtOAc. The extract was washed with H2O and brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with EtOAc–hexane (1:3, v/v) to give 9d (5.7 mg, 62%).
6-Cyano-5-hydroxy-12-phenethylindolo[2,3-a]carbazole (9e) from 8e — In the general procedure C, NaCN (117 mg, 2.27 mmol), 8e (32.3 mg, 0.08 mmol), DMF (2.0 mL), and H2O (1.0 mL) were used. After column-chromatography, 9e (25.8 mg, 85%) was obtained. 9e: mp 255—257˚C (decomp., pale brown powder, recrystallized from acetone). IR (KBr): 3282, 2212, 1628, 1410, 1238, 742, 700 cm-1. 1H-NMR (DMSO-d6) δ: 3.10 (2H, t, J=7.2 Hz), 5.12 (2H, t, J=7.2 Hz ), 7.04—7.08 (1H, m), 7.11 (4H, d, J=4.4 Hz), 7.26 (1H, t, J=7.9 Hz), 7.27 (1H, t, J=7.9 Hz), 7.38 (1H, td, J=7.9, 0.98 Hz), 7.48 (1H, td, J=7.9, 0.98 Hz), 7.54 (1H, d, J=7.9 Hz), 7.72 (1H, d, J=7.9 Hz), 8.34 (1H, d, J=7.9 Hz), 8.45 (1H, d, J=7.9 Hz), 10.7 (1H, br s, disappeared on addition of D2O), 11.6 (1H, s, disappeared on addition of D2O). MS m/z: 401 (M+). Anal. Calcd for C27H19N3O·H2O: C, 77.31; H, 5.05; N, 10.02. Found: C, 77.37; H, 4.85; N, 9.81.
12-(E)-Cinnamyl-6-Cyano-5-hydroxyindolo[2,3-a]carbazole (9f) from 8f — In the general procedure C, NaCN (159 mg, 3.23 mmol), 8f (47.3 mg, 0.10 mmol), DMF (3.0 mL), and H2O (1.5 mL) were used. After column-chromatography, 9f (35.8 mg, 80%) was obtained. 9f: yellow viscous oil. IR (film): 3467, 2216, 1631, 1414, 1173, 741 cm-1. 1H-NMR (DMSO-d6) δ: 5.66 (2H, d, J=5.1 Hz), 6.44 (1H, d, J=15.9 Hz), 6.56 (1H, dt, J=15.9, 5.1 Hz), 7.17 (1H, t, J=7.4 Hz), 7.22 (2H, t, J=7.4 Hz), 7.26 (2H, d, J=7.4 Hz), 7.28 (1H, t, J=7.7 Hz), 7.34 (1H, t, J=7.7 Hz), 7.47 (1H, td, J=7.7, 0.88 Hz), 7.50 (1H, td, J=7.7, 0.88 Hz), 7.71 (1H, d, J=7.7 Hz), 7.77 (1H, d, J=7.7 Hz), 8.41 (1H, d, J=7.7 Hz), 8.45 (1H, d, J=7.7 Hz), 10.8 (1H, br s, disappeared on addition of D2O), 11.6 (1H, s, disappeared on addition of D2O). HR-MS m/z: Calcd for C28H19N3O: 413.1528. Found: 413.1529.
6-Cyano-12-cyanomethyl-5-hydroxyindolo[2,3-a]carbazole (9g) from 8g — In the general procedure C, NaCN (1.45 g, 27.8 mmol), 8g (333 mg, 0.93 mmol), DMF (24.0 mL), and H2O (12.0 mL) were used. After column-chromatography, 9g (168 mg, 54%) was obtained. 9g: mp 272.5—275˚C (decomp., pale gray powder, recrystallized from EtOAc–hexane). IR (KBr): 3300, 2230, 1630, 1580, 1414, 1320, 1178, 902, 745 cm-1. 1H-NMR (DMSO-d6) δ: 6.17 (2H, s), 7.31 (1H, t, J=8.0 Hz), 7.42 (1H, t, J=8.0 Hz), 7.53 (1H, t, J=8.0 Hz), 7.56 (1H, t, J=8.0 Hz), 7.73 (1H, d, J=8.0 Hz), 7.88 (1H, d, J=8.0 Hz), 8.41 (1H, d, J=8.0 Hz), 8.47 (1H, d, J=8.0 Hz), 10.93 (1H, s, disappeared on addition of D2O), 11.90 (1H, s, disappeared on addition of D2O). MS m/z: 336 (M+). Anal. Calcd for C21H12N4O·1/8H2O: C, 74.49; H, 3.65; N, 16.55. Found: C, 74.70; H, 3.62; N, 16.25.
6-Cyano-12-N,N-dimethylcarbamoylmethyl-5-hydroxyindolo[2,3-a]carbazole (9h) from 8h — In the general procedure C, NaCN (119 mg, 2.43 mmol), 8h (33.1 mg, 0.81 mmol), DMF (2.0 mL), and H2O (1.0 mL) were used. After column-chromatography, 9h (29.6 mg, 95%) was obtained. 9h: mp >300˚C (gray powder, recrystallized from MeOH). IR (KBr): 3311, 2216, 1651, 1635, 1412, 742 cm-1. 1H-NMR (DMSO-d6) δ: 2.86 (3H, s), 3.33 (3H, s), 5.75 (2H, s), 7.27 (1H, t, J=7.8 Hz), 7.31 (1H, t, J=7.8 Hz), 7.45 (1H, t, J=7.8 Hz), 7.47 (1H, t, J=7.8 Hz), 7.59 (1H, d, J=7.8 Hz), 7.67 (1H, d, J=7.8 Hz), 8.38 (1H, d, J=7.8 Hz), 8.45 (1H, d, J=7.8 Hz), 10.7 (1H, br s, disappeared on addition of D2O), 11.5 (1H, s, disappeared on addition of D2O). HR-MS m/z: Calcd for C23H18N4O2: 382.1430. Found: 382.1421.
6-Cyano-5-hydroxy-12-methoxycarbonylmethyl- (9i) and 12-Carboxymethyl-6-cyano-5- hydroxyindolo[2,3-a]carbazole (9q) from 8i — In the general procedure C, NaCN (395 mg, 7.64 mmol), 8i (100 mg, 0.25 mmol), DMF (4.0 mL), and H2O (2.0 mL) were used. After column-chromatography, 9i (15.5 mg, 17%) was obtained. The aqueous layer was made acidic by adding aq. 8% HCl and extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a residue, which was column-chromatographed on SiO2 with CHCl3–MeOH–AcOH (46:5:0.5, v/v) to give 9q (38.6 mg, 43%). 9i: mp >300 ˚C (pale gray powder, recrystallized from EtOAc–hexane). IR (KBr): 3410, 2220, 1720, 1630, 1458, 1417, 1240, 1177, 737 cm-1. 1H-NMR (DMSO-d6) δ: 3.69 (3H, s), 5.80 (2H, s), 7.28 (1H, t, J=7.3 Hz), 7.35 (1H, t, J=7.3 Hz), 7.45—7.52 (2H, m), 7.65 (1H, d, J=7.3 Hz), 7.66 (1H, d, J=7.3 Hz), 8.39 (1H, d, J=7.7 Hz), 8.44 (1H, d, J=7.7 Hz), 10.79 (1H, s, disappeared on addition of D2O), 11.65 (1H, s, disappeared on addition of D2O). HR-MS m/z: Calcd for C22H15N3O3: 369.1114. Found: 369.1114. 9q: mp 198—200˚C (decomp., gray powder, recrystallized from MeOH–H2O). IR (KBr): 3367, 2208, 1724, 1631, 1462, 1412, 1323, 1173, 741, 428 cm-1. 1H-NMR (DMSO-d6) δ: 5.64 (2H, s), 7.26 (1H, t, J=7.8 Hz), 7.33 (1H, t, J=7.8 Hz), 7.41—7.51 (2H, m), 7.63 (1H, d, J=8.3 Hz), 7.65 (1H, d, J=8.3 Hz), 8.38 (1H, d, J=7.8 Hz), 8.43 (1H, d, J=7.8 Hz), 10.74 (1H, br s, disappeared on addition of D2O), 11.70 (1H, s, disappeared on addition of D2O). MS m/z: 355 (M+). Anal. Calcd for C21H13N3O3·1/2H2O: C, 69.22; H, 3.87; N, 11.53. Found: C, 69.20; H, 3.92; N, 11.27.
12-(3-Bromopropyl)-6-cyano- (9l) and 6-Cyano-12-(3-cyanopropyl)-5-hydroxyindolo[2,3-a]- carbazole (9r) from 8l — In the general procedure C, NaCN (107 mg, 2.18 mmol), 8l (32.2 mg, 0.07 mmol), DMF (2.0 mL), and H2O (1.0 mL) were used. After column-chromatography, 9l (6.9 mg, 23%) and 9r (6.1 mg, 23%) were obtained in the order of elution. 9l: (brown viscous oil). IR (film): 3423, 2210, 1633, 1454, 1246, 746 cm-1. 1H-NMR (DMSO-d6) δ: 2.40 (2H, q, J=6.9 Hz), 3.56 (2H, t, J=6.9 Hz), 4.95 (2H, t, J=6.9 Hz), 7.28 (1H, t, J=7.7 Hz), 7.34 (1H, t, J=7.7 Hz), 7.49 (1H, td, J=7.7, 1.2 Hz), 7.53 (1H, td, J=7.7, 1.2 Hz), 7.73 (1H, d, J=7.7 Hz), 7.78 (1H, d, J=7.7 Hz), 8.40 (1H, d, J=7.7 Hz), 8.46 (1H, d, J=7.7 Hz), 10.8 (1H, br s, disappeared on addition of D2O), 11.6 (1H, s, disappeared on addition of D2O). HR-MS m/z: Calcd for C22H16N3O81Br: 419.0456. Found: 419.0491. C22H16N3O79Br: 417.0477. Found: 417.0451. 9r: (brown viscous oil). IR (film): 3342, 2262, 2210, 1633, 1452, 1400, 756 cm-1. 1H-NMR (DMSO-d6) δ: 2.19 (2H, q, J=7.3 Hz), 2.61 (2H, t, J=7.3 Hz), 4.89 (2H, t, J=7.3 Hz), 7.28 (1H, t, J=8.0 Hz), 7.34 (1H, t, J=7.7 Hz), 7.49 (1H, t, J=8.0 Hz), 7.53 (1H, t, J=8.0 Hz), 7.72 (1H, d, J=8.0 Hz), 7.77 (1H, d, J=8.0 Hz), 8.40 (1H, d, J=8.0 Hz), 8.46 (1H, d, J=8.0 Hz), 10.8 (1H, s, disappeared on addition of D2O), 11.6 (1H, s, disappeared on addition of D2O). HR-MS m/z: Calcd for C23H16N4O: 364.1324. Found: 364.1324.
6-Cyano-12-[3-(ethoxycarbonyl)propyl]-5-hydroxyindolo[2,3-a]carbazole (9m) from 8m — In the general procedure C, NaCN (301 mg, 5.83 mmol), 8m (84.8 mg, 0.19 mmol), DMF (4.0 mL), and H2O (2.0 mL) were used. After column-chromatography, 9m (53.3 mg, 72%) was obtained. 9m: mp 258—260˚C (pale brown powder, recrystallized from CHCl3). IR (KBr): 3292, 2210, 1711, 1633, 1242, 1169, 741 cm-1. 1H-NMR (DMSO-d6) δ: 1.07 (3H, t, J=7.1 Hz), 2.13 (2H, quin, J=7.2 Hz), 2.41 (2H, t, J=7.2 Hz), 3.95 (2H, q, J=7.1 Hz), 4.86 (2H, t, J=7.2 Hz), 7.28 (1H, t, J=7.8 Hz), 7.33 (1H, t, J=7.8 Hz), 7.49 (1H, td, J=7.8, 1.7 Hz), 7.51 (1H, td, J=7.8, 1.7 Hz), 7.72 (1H, d, J=7.8 Hz), 7.76 (1H, d, J=7.8 Hz), 8.39 (1H, d, J=7.8 Hz), 8.46 (1H, d, J=7.8 Hz), 10.7 (1H, br s, disappeared on addition of D2O), 11.6 (1H, s, disappeared on addition of D2O). MS m/z: 411 (M+). Anal. Calcd for C25H21N3O3·1/2H2O: C, 71.41; H, 5.27; N, 9.99. Found: C, 71.58; H, 5.28; N, 9.78.
12-(Z)-3-Chloroallyl- (9n) and 12-(E)-3-Chloroallyl)-6-cyano-5-hydroxyindolo[2,3-a]carbazole (9o) from 8n and 8o — In the general procedure C, NaCN (208 mg, 4.25 mmol), about 2:1 mixture of 8n and 8o (56.2 mg, 0.14 mmol), DMF (3.0 mL), and H2O (1.5 mL) were used. After repeated column-chromatography, 9n (21.5 mg, 41%) and 9o (7.3 mg, 14%) were obtained in the order of elution. 9n: >300 ˚C (gray powder, recrystallized from EtOAc). IR (KBr): 3454, 2208, 1628, 1412, 742 cm-1. 1H-NMR (DMSO-d6) δ: 5.64 (2H, d, J=6.6 Hz), 6.12 (1H, q, J=6.6 Hz), 6.58 (1H, d, J=6.6 Hz), 7.28 (1H, t, J=7.9 Hz), 7.35 (1H, t, J=7.9 Hz), 7.48 (1H, t, J=7.9 Hz), 7.52 (1H, t, J=7.9 Hz), 7.59 (1H, d, J=7.9 Hz), 7.70 (1H, d, J=7.9 Hz), 8.40 (1H, d, J=7.9 Hz), 8.46 (1H, d, J=7.9 Hz), 10.8 (1H, br s, disappeared on addition of D2O), 11.7 (1H, s, disappeared on addition of D2O). HR-MS (FAB+) m/z: Calcd for C22H15N3O37Cl: 374.0874. Found: 374.0908. C22H15N3O35Cl: 372.0903. Found: 372.0892. 9o: (pale pink viscous oil). IR (film): 3448, 2218, 1630, 1464, 1417, 742 cm-1. 1H-NMR (DMSO-d6) δ: 5.53 (2H, br d, J=6.3 Hz), 6.25 (1H, dt, J=12.9, 6.3 Hz), 6.51 (1H, d, J=12.9 Hz), 7.28 (1H, t, J=7.8 Hz), 7.34 (1H, t, J=7.8 Hz), 7.48 (1H, td, J=7.8, 1.7 Hz), 7.51 (1H, td, J=7.8, 1.7 Hz), 7.71 (1H, d, J=7.8 Hz), 7.77 (1H, d, J=7.8 Hz), 8.40 (1H, d, J=7.8 Hz), 8.45 (1H, d, J=7.8 Hz), 10.8 (1H, br s, disappeared on addition of D2O), 11.6 (1H, br s, disappeared on addition of D2O). HR-MS m/z: Calcd for C22H14N3O37Cl: 373.0796. Found: 373.0790. C22H14N3O35Cl: 371.0825.Found: 371.0819.
6-Cyano-5-hydroxyindolo[2,3-a]carbazole (10) and (6R*,6aR*,11aR*)-6-chloro-11a-cyano-6a- hydroxy-5,6,6a,11,11a,12-hexahydroindolo[2,3-a]carbazole-5-one (11) from 8p — In the general procedure C, NaCN (109 mg, 2.23 mmol), 8p (27.1 mg, 0.74 mmol), DMF (2.0 mL), and H2O (1.0 mL) were used. After repeated column-chromatography with EtOAc–hexane (1:2, v/v) and CHCl3–MeOH (99:1, v/v), 10 (19.2 mg, 74%) and 11 (5.6 mg, 22%) were obtained in the order of elution. 10: mp >300˚C (pale gray powder, recrystallized from CHCl3). IR (KBr): 3373, 2208, 1646, 1569, 1389, 1351, 1324, 1236, 743 cm-1. 1H-NMR (DMSO-d6) δ: 7.25 (1H, td, J=0.9, 7.8 Hz), 7.28 (1H, d, J=7.8 Hz), 7.42—7.47 (2H, m), 7.73 (2H, ddd, J=0.9, 5.9, 6.7 Hz), 8.33 (1H, d, J=7.8 Hz), 8.39 (1H, d, J=7.8 Hz), 10.62 (1H, br s, disappeared on addition of D2O), 11.62 (1H, br s, disappeared on addition of D2O), 11.59 (1H, s, disappeared on addition of D2O). Anal. Calcd for C19H11N3O: C, 76.76; H, 3.73; N, 14.13. Found: C, 76.81; H, 3.63; N, 14.12. 11: mp 231—233˚C (yellow prisms, recrystallized from CHCl3). IR (KBr): 3465, 2219 (very weak), 1673, 1468, 773 cm-1. 1H-NMR (DMSO-d6) δ: 5.17 (1H, br s, disappeared on addition of D2O), 6.79 (1H, d, J=7.7 Hz), 6.85 (1H, td, J=7.7, 1.2 Hz), 7.20 (1H, td, J=7.7, 1.2 Hz), 7.27 (1H, td, J=7.7, 1.2 Hz), 7.35 (1H, td, J=7.7, 1.2 Hz), 7.37 (1H, s, disappeared on addition of D2O), 7.42 (1H, s, disappeared on addition of D2O), 7.47 (1H, d, J=7.7 Hz), 7.63 (1H, d, J=7.7 Hz), 7.95 (1H, d, J=7.7 Hz), 12.6 (1H, br s, disappeared on addition of D2O). HR-MS (FAB+) m/z: Calcd for C13H12N3O237Cl: 352.0667. Found: 352.0701. C13H12N3O235Cl: 350.697. Found: 350.0703. Anal. Calcd for C13H12N3O2Cl·1/2CHCl3: C, 57.20; H, 3.08; N, 10.26. Found: C, 56.94; H, 3.12; N, 9.99.
6-Cyano-5-hydroxyindolo[2,3-a]carbazole (10) from 8k — In the general procedure C, NaCN (11.2 mg, 3.23 mmol), 8k (47.3 mg, 0.10 mmol), DMF (2.0 mL), and H2O (0.1 mL) were used. After column-chromatography, unreacted 8k (5.5 mg, 16%) and 10 (6.1 mg, 27%) were obtained in the order of elution.
(5R*,6S*,6aR*,11aR*)-6-Chloro-11a-cyano-5,6a-dihydroxy-5,6,6a,11,11a,12-hexahydroindolo[2,3- a]carbazole (12a) from 11 — NaBH4 (4.5 mg, 0.12 mmol) was added to a solution of 11 (14.1 mg, 0.04 mmol) in MeOH (2.0 mL), and the mixture was stirred for 1.5 h at rt. After addition of H2O, the whole was extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave a residue, which was column-chromatographed on SiO2 with EtOAc–hexane (1:3, v/v) to give 12a (6.6 mg, 47%) and unreacted 11 (7.5 mg, 53 %) in the order of elution. 12a: yellow viscous oil. IR (film): 3342, 2235 (almost invisible), 1655, 1585, 748 cm-1. 1H-NMR (DMSO-d6) δ: 3.93 (1H, d, J=8.5 Hz), 5.06 (1H, t, J=8.5 Hz, collapsed to d on addition of D2O), 5.72 (1H, t, J=8.5 Hz, disappeared on addition of D2O), 6.83 (1H, d, J=7.5 Hz), 6.87 (1H, td, J=7.5, 1.3 Hz), 7.06 (1H, t, J=7.5 Hz), 7.13 (1H, s, disappeared on addition of D2O), 7.15 (1H, s, disappeared on addition of D2O), 7.19 (1H, td, J=7.5, 1.3 Hz), 7.21 (1H, td, J=7.5, 1.3 Hz), 7.48 (1H, d, J=7.5 Hz), 7.51 (1H, d, J=7.5 Hz), 7.81 (1H, d, J=7.5 Hz), 11.3 (1H, s, disappeared on addition of D2O). HR-MS (FAB+) m/z: Calcd for C19H15N3O237Cl: 354.0824. Found: 354.0871. C19H15N3O235Cl: 352.0853. Found: 352.0846.
(5R*,6S*,6aR*,11aR*)-6-Chloro-11a-cyano-5,12-diacetyl-6a-hydroxy-5,6,6a,11,11a,12-hexahydro- indolo[2,3-a]carbazole (12b) from 12a — Ac2O (1.0 mL) was added to a solution of 12a (10.0 mg, 0.03 mmol) in pyridine (2.0 mL), and the mixture was stirred for 14 h at rt. After evaporation of the solvent under reduced pressure, the residue was column-chromatographed on SiO2 with EtOAc–hexane (1:3, v/v) to give 12b (3.7 mg, 30%) and unreacted 12a (5.7 mg, 57 %) were obtained in the order of elution. 12b: pale yellow oil. IR (film): 3390, 1749, 1705, 1610, 1373, 744 cm-1. 1H-NMR (DMSO-d6 + 5% D2O, 90°C) δ: 2.13 (3H, s), 2.96 (3H, s), 4.41 (1H, d, J=8.3 Hz), 6.56 (1H, d, J=8.3 Hz), 6.90 (1H, td, J=7.5, 1.7 Hz), 6.97 (1H, d, J=7.5 Hz), 7.24 (1H, td, J=7.5, 1.7 Hz), 7.37—7.42 (2H, m), 7.48 (1H, d, J=7.5 Hz), 7.52 (1H, td, J=7.5, 1.7 Hz), 7.94 (1H, d, J=7.5 Hz). HR-MS (FAB+) m/z: Calcd for C23H19N3O437Cl: 438.1035. Found: 438.1040. C23H19N3O435Cl: 436.1004. Found: 436.1051.
12-Benzyl-6-cyano-5-methoxyindolo[2,3-a]carbazole (13) from 9d — Excess amount of ethereal CH2N2 was added to a solution of 9d (88.0 mg, 0.22 mmol) in MeOH (6.0 mL) and the mixture was stirred for 1.5 h at rt. The solvent was evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with CHCl3–MeOH–28% aq. NH3 (46:0.5:0.05, v/v) to give 13 (75.1 mg, 82%). 13: mp 228.0—228.5˚C (colorless needles, recrystallized from EtOAc). IR (KBr): 3338, 2208, 1628, 1560, 1390, 741 cm-1. 1H-NMR (DMSO-d6) δ: 4.26 (3H, s), 6.16 (2H, s), 7.19 (2H, t, J=7.7 Hz), 7.20 (1H, t, J=7.7 Hz ), 7.24 (1H, d, J=7.7 Hz), 7.26 (1H, d, J=7.7 Hz), 7.33 (1H, t, J=7.4 Hz), 7.38 (1H, t, J=7.4 Hz), 7.50 (1H, td, J=7.4, 1.9 Hz), 7.51 (1H, td, J=7.4, 1.9 Hz), 7.69 (1H, d, J=7.4 Hz), 7.71 (1H, d, J=7.4 Hz), 8.29 (1H, d, J=7.4 Hz), 8.48 (1H, d, J=7.4 Hz), 11.9 (1H, s, disappeared on addition of D2O). MS m/z: 401 (M+). Anal. Calcd for C27H19N3O·1/2H2O: C, 79.00; H, 4.91; N, 10.24. Found: C, 79.09; H, 4.90; N, 9.99.
6-(Z)-Aminomethylidene-12-n-butyl-5,6,11,12-tetrahydroindolo[2,3-a]carbazole-5-one (15a) from 9a — General Procedure D: A 1.0 M solution of DIBAL in toluene (2.7 mL, 2.67 mmol) was added to a solution of 9a (31.4 mg, 0.09 mmol) in anhydrous THF (2.0 mL) under ice cooling and the mixture was stirred under N2 atmosphere at rt for 3 h. After addition of MeOH and aq. Rochelle salt, the whole was extracted with EtOAc. The extract was washed with brine, dried over Na2SO4, and evaporated under reduced pressure to leave an oil, which was column-chromatographed on SiO2 with CHCl3–MeOH (99:1, v/v) to give 15a (23.0 mg, 73%). 15a: mp 170—172˚C (decomp., dark yellow prisms, recrystallized from EtOAc). IR (KBr): 3400, 1628, 1610, 1577, 1560, 1421, 737 cm-1. 1H-NMR (DMSO-d6) δ: 0.82 (3H, t, J=7.4 Hz), 1.29 (2H, sex, J=7.4 Hz), 1.81 (2H, quin, J=7.4 Hz), 4.77 (2H, t, J=7.4 Hz), 7.14 (1H, td, J=7.8, 1.2 Hz), 7.22 (1H, t, J=7.8 Hz), 7.29 (1H, t, J=7.8 Hz), 7.31 (1H, td, J=7.8, 1.2 Hz), 7.62 (1H, d, J=7.8 Hz), 7.63 (1H, d, J=7.8 Hz), 8.02 (1H, d, J=7.8 Hz), 8.47 (1H, d, J=7.8 Hz), 8.60 (1H, br t, J=8.2 Hz, disappeared on addition of D2O), 8.84 (1H, dd, J=13.8, 8.2 Hz, collapsed to s on addition of D2O), 11.1 (1H, s, disappeared on addition of D2O), 12.0 (1H, dd, J=13.8, 8.2 Hz, disappeared on addition of D2O). HR-MS m/z: Calcd for C23H21N3O: 355.1685. Found: 355.1693.
6-(Z)-Aminomethylidene-12-n-benzyl-5,6,11,12-tetrahydroindolo[2,3-a]carbazole-5-one (15b) from 9d — In the general procedure D, DIBAL (1.4 mL, 1.45 mmol), 9d (18.7 mg, 0.05 mmol), THF (2.0 mL) were used. The reaction time was 19 h. After column-chromatography, 15b (6.9 mg, 47%) was obtained. 15b: mp 207—209˚C (decomp., yellow powder, recrystallized from EtOAc). IR (KBr): 3450, 1628, 1610, 1577, 1560, 1410, 742 cm-1. 1H-NMR (DMSO-d6) δ: 6.04 (2H, s), 7.12—7.28 (9H, m), 7.53 (1H, d, J=7.5 Hz), 7.54 (1H, d, J=7.5 Hz), 8.04 (1H, d, J=7.5 Hz), 8.49 (1H, dd, J=7.5, 1.7 Hz), 8.68 (1H, br t, J=8.4 Hz, disappeared on addition of D2O), 8.88 (1H, dd, J=13.6, 8.4 Hz, collapsed to s on addition of D2O), 11.2 (1H, s, disappeared on addition of D2O), 12.1 (1H, dd, J=13.6, 8.4 Hz, disappeared on addition of D2O). HR-MS (FAB+) m/z: Calcd for C26H20N3O: 390.1606. Found: 390.1631.
6-Acetoaminomethylidene-12-n-butyl-5,6,11,12-tetrahydroindolo[2,3-a]carbazole-5-one (16) from 15a — Ac2O (0.75 mL) was added to a solution of 15a (16.1 mg, 0.05 mmol) in pyridine (1.5 mL), and the mixture was stirred for 1.5 h at rt. After evaporation of the solvent under reduced pressure, the residue was column-chromatographed on SiO2 successively with EtOAc–hexane (1:3, v/v) and CHCl3–MeOH–28% aq. NH3 (46:0.5:0.05, v/v) to give 16 (15.7 mg, 87%). 16: red viscous oil. IR (film): 3354, 1685, 1620, 1610, 1552, 1415, 1273, 752, 739 cm-1. 1H-NMR (CDCl3) δ: 0.92 (3H, t, J=7.5 Hz), 1.37 (2H, sex, J=7.5 Hz), 1.81 (2H, quin, J=7.5 Hz), 2.28 (3H, s), 4.02 (2H, t, J=7.5 Hz), 7.17 (1H, dd, J=7.3, 1.6 Hz), 7.25 (1H, td, J=7.3, 1.6 Hz), 7.30 (1H, td, J=7.3, 1.6 Hz), 7.32 (1H, td, J=7.3, 1.6 Hz), 7.34 (1H, td, J=7.3, 1.6 Hz), 7.42 (1H, d, J=7.3 Hz), 7.91 (1H, d, J=7.3 Hz), 8.24 (1H, s, disappeared on addition of D2O), 8.44 (1H, dd, J=7.3, 1.6 Hz), 8.59 (1H, d, J=10.4 Hz, collapsed to s on addition of D2O), 13.4 (1H, d, J=10.4 Hz, disappeared on addition of D2O). HR-MS m/z: Calcd for C25H23N3O2: 397.1791. Found: 397.1790.
X-Ray Crystallographic Analysis of 9a and 11— All measurements were made on a Rigaku AFC5R diffract meter with graphite monochromated Cu-Kα radiation (λ=1.54178 Å). The structure was solved by direct methods using MITHRIL.9 Non-hydrogen atoms were refined anisotropically.
9a: a single crystal (0.20x0.20x0.30 mm) was obtained by recrystallization from EtOAc. Crystal data: C23H19N3O·C4H8O2, M=441.53, triclinic, space group P1– (#2), a=10.626 (1)Å, b=12.276 (1)Å, c=9.912 (1)Å, α=104.474 (8)°, β=110.402 (9)°, γ=81.84 (1)°, V=1431.8 (2)Å3, Z=2, Dcalc=1.252 g/cm3, F(000)=468, and µ(CuKα)=6.26 cm–1. The final cycle of full-matrix least-squares refinement was based on 2807 observed reflections (I >3.00σ (I), 2θ < 120.2°) and 386 variable parameters. The final refinement converged with R=0.049 and Rw=0.059.
11: a single crystal (0.20x0.10x0.20 mm) was obtained by recrystallization from CHCl3. Crystal data: C19H12N3O2, M=349.78, monoclinic, space group P21/a (#14), a=14.408 (5)Å, b=14.096 (3)Å, c=17.928 (4)Å, β=93.60 (2)°, V=3634 (2)Å3, Z=8, Dcalc=1.278 g/cm3, F(000)=1440, and µ(CuKα)=20.08 cm–1.
The final cycle of full-matrix least-squares refinement was based on 2139 observed reflections (I >3.00σ (I), 2θ < 120.4°) and 583 variable parameters. The final refinement converged with R=0.085 and Rw=0.091.

References

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