HCID 19358398, compound → Indole

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-iodo-4-(N-(methyl)aminosulphonylmethyl)phenyl aniline (10 g, 30.7 mmol), 1,4-bis-triethylsilyl-3-butyn-1-ol (10.97 g, 36.8 mmol) sodium carbonate (16.26 g, 153.4 mmol) and anhydrous DMF (500 ml) was degassed with N2 for 0.5 h. Pd(OAc)2 (0.7 g, 3.1 mmol) was added and the mixture heated at 100° C. for 6 h. The DMF was removed under vacuum and the residue partitioned between EtOAc (250 ml) and water (250 ml). The solutions were passed through celite to remove insolubles and the aqueous layer separated and extracted further with ethyl acetate (4×200 ml). The combined organics were dried (Na2SO4) and evaporated. The residue was dissolved in methanol (100 ml) and 5N hydrochloric acid (30 ml) was added. The mixture was stirred at room temperature for 2 h and the solvent then removed under vacuum and the residue neutralised with saturated K2CO3 solution. The aqueous was extracted with EtOAc (200 ml) and n-butanol (2×200 ml) and the combined extracts evaporated under vacuum The residue was chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (60:8:1) to give the title-indole (5.39 g, 66%), mp 114-116° C., δ (250 MHz, D6 -DMSO) 2.54 (3H, d, J=4.8Hz, MeNH), 2.83 (2H, t, J=7.5Hz, CH2), 3.60-3.69 (2H, m, CH2 --OH), 4.34 (2H, s, CH2), 4.65 (1H, t, J=5.4Hz, OH), 6.78 (1H, q, J=4.8Hz, MeNH), 7.06 (1H, dd, J=2.2 and 8.3Hz, Ar--H), 7.16 (1H, d, J=2.2Hz, Ar--H), 7.31 (1H, d, J=8.3Hz, Ar--H), 7.51 (1H, s, Ar--H), 10.86 (1H, s, NH).

Provenance & Evidence