Methanone, [3-[(dimethylamino)methyl]-1H-indol-1-yl]-10H-phenothiazin-10-yl- synthesis

Yield:1417560-80-5 11%

Reaction Conditions:

with dmap;triethylamine in dichloromethane at 20; for 72 h;Inert atmosphere;

Steps:

N,N-Dimethyl-N-{[1-(10H-phenothiazin-10-ylcarbonyl)-1H-indol-3-yl]methyl}amine (43)

General procedure: The 10H-phenothiazine-10-carbonyl chloride 44 (1.05 equiv) was dissolved in CH₂Cl₂ under inert atmosphere and added to a mixture of the corresponding indole derivative 45 or 46 (1 equiv), 4-dimethylaminopyridine (DMAP) (0.1 equiv) and Et₃N (1.3 equiv) in CH₂Cl₂. The resulting mixture was stirred for 72 hours under inert atmosphere at rt, quenched with saturated aqueous NH₄Cl solution, and washed several times with water and brine. The organic phase was dried over MgSO₄, filtrated, and the solvent evaporated in vacuo. The obtained residue was purified by column chromatography on silica gel (EtOAc/n-heptane 5/5) to provide pure compound 42 or 43. White solid; mp 174-176°C; 11% yield. ¹HNMR (CDCl₃, 400 MHz) δ (ppm) 2.02 (s, 6H, N(CH₃)₂),3.31 (s, 2H, CH₂N(CH₃)₂),6.67 (s, 1H, ArH), 7.15-7.20 (m, 4H,ArH), 7.20-7.25 (m, 1H, ArH), 7.36 (td, J = 7.8, 1.2 Hz, 1H, ArH),7.43-7.47 (m, 2H, ArH), 7.58-7.63 (m,3H, ArH), 8.17 (d, J = 8.2 Hz, 1H, ArH). ¹³C NMR (CDCl₃, 100 MHz) δ(ppm) 45.1 (2CH₃), 54.2 (CH₂), 114.4 (CH), 119.7 (CH),122.7 (CH), 124.4 (CH), 124.7 (2CH), 125.1 (C), 125.2 (CH), 126.4 (2CH), 127.7(2CH), 127.9 (2CH), 129.8 (C), 131.4 (2C), 136.7 (C), 139.9 (2C), 150.7 (C). Anal. calcd for C₂₄H₂₁N₃OS: C, 72.15; H, 5.30; N, 10.52. Found: C, 72.49; H, 5.56; N, 10.38%.

References:

Abuhaie, Cristina-Maria;B?cu, Elena;Rigo, Beno?t;Gautret, Philippe;Belei, Dalila;Farce, Amaury;Dubois, Jo?lle;Ghinet, Alina [Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,# 1,p. 147 - 152] Location in patent:supporting information