1-Methyl-5-nitroindazole

General procedure: Cesium carbonate (12.26mmol) was added to a solution of 5-nitroindazole 1 (6.13 mmol) in tetrahydrofuran (THF;25mL)cooledat 0°C. After 15 mn at 0°C, MeI or allyl bromide(6.13mmol) was added dropwise. Upon disappearance of the starting materialas indicated by TLC, the resulting mixture was evaporated.The crude material was dissolved with EtOAc(50mL), washed with water and brine, and dried over MgSO4; and the solvent was removed in vacuo.The resulting residue was purified by column chromatography on silica gel using EtOAc=hexane(3:7) to afford the desired products, 1-alkyl-5-nitroindazole followed by2-alkyl-5-nitroindazole.NaH (1.47 g, 36.8 mmol) was added to THF (40 mL) at 0° C. Separately, 5-nitroindazole (5.0 g, 30.6 mmol) was dissolved in THF (30 mL), and the mixed solution was slowly added to the prepared solution. Iodomethane (2.1 mL, 33.7 mmol) was added to the reaction solution at the same temperature, followed by stirring for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, and added with water and ethyl acetate. The reaction mixture was added with distilled water for quenching, diluted with ethyl acetate, and washed with distilled water. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrated compound (1-methyl added (RSodium hydride (55.0 mmol) was added to a solution of 5-nitro-1H-indazole (18.40 mmol) inN, N-dimethylformamide (50 mL) and the mixture was maintained for 60 min at 0 °C. To the mixture was added Methyl iodide (22.12 mmol) was added and the reaction mixture was allowed to warm to rt and was maintained for 18 h. The reaction mixture was quenched with water (60 mL), filtered through Celite, and the filtrate was concentrated to provide l-methyl-5-nitro-1H-indazole in 83percent yield as a yellow solid.Intermediate 40: Synthesis of l-methyl-lH-indazole-5-sulfonyl chloride.1. Synthesis of 1 -methγl-5-nitro- lH-indazole.Sodium hydride (55.0 mmol) was added to a solution of 5-nitro-lH-indazole (18.40 mmol) in N.jV-dimethylformamide (50 mL) and the mixture was maintained for 60 min at 0 Intermediate 40: Synthesis of l-methyl-l//-indazole-5-sulfonyl chloride. 1. Synthesis of l-methyl-5-nitro-lH-indazole.Sodium hydride (55.0 mmol) was added to a solution of 5-nitro-lH-indazole (18.40 mmol) in N, N-dimethylformamide (50 mL) and the mixture was maintained for 60 min at 0 Step 1: Preparation of l-methyl-5-nitro-lH-indazoleSodium hydride (5.40 g, 0.135 mol) is added portionwise to a solution of 5- nitroindazole (20.0 g, 0.122 mol) in DMF (250 mL) at room temperature. The reaction is NaH (1.47 g, 36.8 mmol) was added to THF (40 mL) at 0°C. Separately, 5- nitroindazole (5.0 g, 30.6 mmol) was dissolved in THF (30 mL), and the mixed solution was slowly added to the prepared solution. Iodomethane (2.1 mL, 33.7 mmol) was added to the reaction solution at the same temperature, followed by stirring for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, and added with water and ethyl acetate. The reaction mixture was added with distilled water for quenching, diluted with ethyl acetate, and washed with distilled water. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The concentrated compound (1 -methyl added (RGeneral procedure: Procedure E: NaH (1.1 equiv) was added to the solution of amine (1 equiv) in anhydrous N, N-dimethylformamide. Iodomethane (1.1 equiv) was added dropwise to the reaction mixture at 0°C.The reaction was continued at room temperature until the starting material was consumed. The resulting mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried over MgSOGeneral procedure: A mixture of 3-amino-1-methyl-1H-indazole 2 (3.0 mmol) and tert-butyl nitrite (1.0 mL, 8.1 mmol, 2.7 equiv) in THF (12.0 mL) was heated to reflux for 1 h. The mixture was cooled to rt and then concentrated. H2O (10.0 mL) and EtOAc (20.0 mL) were added to the residue. The organic layer was washed with H2O (10.0 mL), brine (10.0 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to silica-gel chromatography by using Et2O/hexanes (1:4) as eluent to give the product 3.#10;To a solution of 9.78 g (60 mmol) of 1-methyl-1H-indazole in 20 mL of dimethylsulfoxide were successively added 3.53 g (63 mmol) of powdered KOH and 8.52 g (60 mmol) of methyl iodide. The mixture was stirred at room temperature for 3 h, after which it was diluted with 200 mL of water. The precipitate was separated and crystallized from 2-propanol. Yield 9.45 g (mixture of isomers), yellowish crystals.General procedure: 1-alkyl-5-nitro-1H-indazoles 1a-d (10 mmol) and 1-naphthylacetonitrile (2) (13 mmol) were added with stirring to a solution of KOH(20 g, 357 mmol) in methanol (40 mL). The mixture was stirred at r.t. for 48 h. After concentration at reduced pressure, the precipitate wascollected by filtration, washed with water, followed by cold EtOH and acetone, and then air dried to give the crude products 3a-d. Further purification was achieved by crystallisation from a suitable solvent such as EtOH or acetone. 3-Methyl-3H-benzo[a]pyrazolo[3, 4-j]acridine-13-carbonitrile(3a): Shiny yellow needles (acetone); m.p. 320-322 C; yield 73%;IR (KBr) (numax cm-1): 2223 (CN); 1H NMR (300 MHz, CDCl3): delta 4.17(3H, s, NCH3), 7.78-7.99 (7H, m, ArH), 8.09 (1H, d, J = 9.3 Hz, ArH), 9.42 (1H, s, ArH), 9.98 (1H, d, J = 7.5 Hz, ArH); 13C NMR (75 MHz, CDCl3): delta 36.2, 107.3, 115.3, 116.4, 120.5, 123.2, 124.1, 126.0, 127.5, 128.1, 128.3, 129.0, 129.3, 129.3, 132.5, 133.4, 135.5, 137.4, 145.7, 147.6; MS (m/z) 308 [M]+ found: C, 78.05; H, 3.94; N, 17.90; calcd forC20H12N4 (308.3): C, 77.91; H, 3.92; N, 18.17%.

Molecular Weight:177.16
XLogP3:2
Hydrogen Bond Acceptor Count:3
Exact Mass:177.053826475
Monoisotopic Mass:177.053826475
Topological Polar Surface Area:63.6
Heavy Atom Count:13
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes