Ciclindole synthesis

Yield:32211-97-5 50%

Reaction Conditions:

with sulfuric acid in water at 95 - 100;

Steps:

N,N-Dimethyl-(2,3,4,9-tetrahydro-1H-carbazole-3-yl)amine (13a).

General procedure: Aqueous sulfuric acid solution (10 % w/v, 30 mL) was taken in a round bottom flask, added (1,4-dioxa-spiro[4.5]dec-8-yl)dimethylamine (12a, 1.5 g, 8.1 mmol) followed by phenylhydrazine (1.52 g, 14.08 mmol) at room temperature. The reaction mass was heated to reflux temperature (95-100 °C) and maintained reflux for 2-3 h. The progress of the reaction was monitored by TLC. After completion of reaction, the reaction mass was cooled to 10-15 °C. Then the mass was basified with aqueous sodium hydroxide solution (20 % w/v) and the aqueous layer was extracted with ethyl acetate. Organic layer was washed with brine solution, dried over anhydrous sodium sulfate and organic volatiles were removed by distillation under vacuum. The crude compound was purified by flash chromatography (ethyl acetate: triethylamine 9:0.2) to obtain 0.8 g of title compound (13a), the yield being 50 %. HPLC (%): 98.10, mp (°C): 132.8-139.1; IR (cm-1): 3143, 3054, 2921, 2828, 2729, 1623, 1585, 741; ESI-MS (m/z): 215.1 (M+H)+; 1H-NMR (400 MHz, CDCl3): d 1.80-1.85 (m, 1H, C2-H), 2.20-2.23 (m, 1H, C2-H), 2.45 (s, 6H, N-(CH3)2), 2.64-2.67 (m, 1H, C4-H), 2.77-2.85 (m, 3H, C1, C3-H), 2.95-3.00 (m, 1H, C4-H), 7.07-7.15 (m, 2H, C6, C7-H), 7.27-7.29 (d, 1H, J = 8.02 Hz, C5-H) 7.46-7.48 (d, 1H, J = 7.4 Hz, C8-H), 7.88 (bs, 1H, NH).

References:

Nirogi, Ramakrishna V. S.;Konda, Jagadishu Babu;Kambhampati, Ramasastry;Shinde, Anil;Bandyala, Thrinath Reddy;Gudla, Parandhama;Kandukuri, Kiran Kumar;Jayarajan, Pradeep;Kandikere, Vishwottam;Dubey, P. K. [Bioorganic and medicinal chemistry letters,2012,vol. 22,# 22,p. 6980 - 6985,6] Location in patent:supporting information