, 39 (m, J = 8.18 Hz, J = 1.02 Hz, 1H) Anal. (C 28 H 36 N 4 O 3 ) C, H, N. 1-sec-Butyl-N-[[1-(2-phenylethyl)-4-piperidinyl]methyl]-1H-inda- zole-3-carboxamide (11n). 11l (15.8 g, 44 mmol) was added into a stirred suspension of NaH (1.76 g, 60% suspension in mineral oil) in DMF (100 mL) cooled at 0 °C. The mixture was stirred at room temperature for 1 h, and then 2-bromobutane (6 mL, 44 mmol) was added. After 24 h at the same temperature, water (200 mL) was added, the solution was filtered, and the solid was dissolved in ethyl acetate. The residual inorganic material was filtered off, and the solution was concentrated under vacuum and treated with Et 2 O/HCl. The hydrochloride that formed was recrystallized from ethanol IR (KBr): ? 3327, 1H), pp.7-22
, 13 C NMR (DMSO-d 6 ): ? 22 2-Methyl-2H-pyrrolo[3,4-c]quinolin-4(5H)-one (25) Methyl iodide (1.5 g, 11 mmol) and anhydrous potassium carbonate (1.5 g, 11 mmol) were added into a solution of 24 (2.0 g, 11 mmol) in anhydrous DMF (10 mL) The mixture was stirred at 90 °C for 15 h. After cooling, the reaction mixture was treated with water (30 mL) and filtered. The solid obtained was purified by column chromatography on silica gel (chloroform/methanol mixture (10:1) as eluent) to give 1.0 g of 25 (46%, sublimes at 225 °C, from toluene). 1 H NMR Journal of Medicinal Chemistry Article dx.doi.org/10)-one (26) To a solution of 24 (3.0 g, 16 mmol) in dioxane (150 mL) brought to reflux was added potassium metal (580 mg, 15 mmol), and the mixture was stirred at reflux until total disappearance of the metal was observed (2 h) After cooling, 2-iodopropane (2.8 g, 16 mmol) and 18-crown-6 ether (3.9 g, 15 mmol) were added, and the mixture was refluxed for 5.5 h. A further portion of 2-iodopropane (1.4 g, 8.1 mmol) was then added, and the reaction mixture was stirred at reflux for a further 15 h. After cooling, the dioxane was removed under reduced pressure, and the residue was taken up in ethyl acetate (100 mL) and washed with brine (3 × 50 mL) The organic solution was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain a crude product, which was purified by column chromatography of aluminum oxide (ethyl acetate as eluent, Crude 11o was treated with 2.5 N HCl in ethanol solution to give the corresponding hydrochloride 4.50 (t, J = 7.31 Hz, 2H), 2.63?4.04 (m, 10H), 1.26?2.27 (m, 8H), 0.94 (d, J = 6.21 Hz, 6H)09. Anal. (C 27 H 36 N 4 O·HCl) 9446?9466 (DMSO-d 6 ): ? 3.91 (s, 3H), 7.09?7.25 (m, 3H), 7.58?7.81 (m, 3H), 10.73 (s, 1H). Anal. (C 12 H 10 N 2 O) C, H 1H). Anal. (C 14 H 14 N 2 O) C, H, N. 1-Acetyl-N-[[1-(2-phenylethyl)-4-piperidinyl]methyl]-1H-inda- zole-3-carboxamide (11p). Acetic anhydride (0.26 mL, 2.75 mmol) was added into a suspension of 11l (500 mg, 1.4 mmol) in CH 2 Cl, p.51607762, 1021.
, 93 (m, J = 7.7 Hz, J = 1.2 Hz, 1H) Anal, The product was converted to the hydrochloride as described for the compound 12e (95%, 165?167 °C, from diisopropyl ether
, Acid (12g). 12g was prepared according to the procedure described for 11ab using ethanol as solvent (27%, 155? 166 °C, from ethanol) 1 H NMR (DMF-d 7 ): ? 108 (m, 1H), 14?16 (br s, 1H))oxy]methyl]-1- piperidinyl]ethyl]benzoic Acid (12h). 12h was prepared according to the procedure described for 11ab using ethanol as solvent (dd, 1 H). Anal A solution of ethyl 3-(2-nitrophenyl)propanoate (22) 35 (26.6 g, 120 mmol) and TosMIC (25.4 g, 130 mmol) in anhydrous dimethyl sulfoxide/ethyl ether (1:2; 450 mL) was added dropwise to a well-stirred suspension of 60% sodium hydride in paraffin (10.4 g, 260 mmol) in anhydrous ethyl ether (300 mL) under a stream of argon. After the addition, the mixture was stirred at room temperature for 25 min, water (500 mL) was then added, and the resulting solution was extracted, 2H), 1.93 (m, 3H), 2.23 (m, 2H), 2.74 (m, 2H), 2.97 (m, 2H), 3.17 (m, 2H), 3.25 (m, 2H), 4.13 (s, 3H), 4.48 (d, 2H), 7.36 (m, 1H), 7.43 (m, 1H)50%, 165 °C, from ethyl acetate). 1 H NMR (DMF-d 7 ): ? 1.30 (m, 2H), 1.51 (m, 2H), 1.79?1.82 (m, 1 H), 2.51 (m, 5H):1) as eluent) to give 12.8 g of 23 (41%, 159?161 °C, from ethanol). 1 H NMR (CDCl 3 ): ? 2.51 (m, 3H), 4.01 (q, 2H), 6.51 (m, 1H), 7.31?7.33 (m, 1H), 7.39?7.41 (m, 2H), 7.49?7.53 (m, 1H), pp.1-08, 2002.
, Anal Iron powder (6.7 g, 120 mmol) was added over 15 min into a solution0 g, 7.7 mmol) in glacial acetic acid (100 mL) mechanically stirred at 85 °C. The mixture was stirring at the same temperature for 45 min After cooling, the iron was removed by filtration and washed several times with tetrahydrofuran, and the filtrate was evaporated under reduced pressure. The crude product was purified by column chromatography on aluminum oxide (ethyl acetate as eluent) to give 1.1 g of 24 (77%, sublimes at 280 °C from ethanol). 1 H NMR (DMSO-d 6 ): ? 7 (s, 1H). Anal. (C 11 H 8 N 2 O) C, H, N. 4-Chloro-2-methyl-2H-pyrrolo A mixture of product, 92?7.9405?7.28 (m, 3H), 7.57?7.63 (m, 2H), 7.84?7.88 (m, 1H), 10.7 (s, 1H) phosphorus oxychloride (16.2 mL), and triethylamine (1.2 mL) was stirred at 120 °C for 6 h. After cooling, the reaction mixture was poured cautiously into ice and extracted with Journal of Medicinal Chemistry, pp.9446-9466, 2012.
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