3-Bromoaniline → 4-N-(3-bromophenyl)-9H-pyrimido[4,5-b]indole-2,4-diamine

Participants

Reaction Steps

A mixture of 2-amino-4-chloroindolo[2,3-d]pyrimidine hydrochloride (123 mg, 0.6 mmol) and 3-bromoaniline (0.3 mL, 2.8 mmol) in 2-propanol (6 mL) is heated at reflux for 4 hr, filtered through a celite pad, and concentrated in vacuo. The residue is partitioned between ethyl acetate (25 mL) and water (25 mL). The aqueous phase is extracted with further ethyl acetate (2×20 mL), followed by washing the combined extracts with 1% aqueous sodium hydroxide (25 mL), water (2×40 mL) , saturated brine (40 mL), and drying (Na2SO4). The solution is evaporated to dryness under reduced pressure to afford 105 mg crude product as a tan powder. The solid is dissolved in a minimum amount of methanol, filtered, and further purified by preparative plate chromatography (SiO2; 1:1, EtOAc:CH2Cl2; Rf=0.40). After extraction of the product from the silica gel with ethyl acetate, the volume of the warm solution is reduced to minimum, an d it is filtered through celite, and the solvent is removed under reduced pressure. The oily solid thus obtained is dissolved in a minimum amount of 2-propanol and allowed to crystallize at 3 C. over an 18 h period. The crystals are collected by suction filtration, washed with a small amount of cold 2-propanol, and dried in vacuo to give 2-amino-4-(3-bromoanilino)indolo[2,3-d]pyrimidine (34 mg, 17%). 1HNMR, (DMSO): δbrs), 8.57 (1H, s), 8.11 (1H, d, J=8.0 Hz), 8.01 (1H, s), 7.94 (1H, d, J=8.2 Hz), 7.34-7.12 (5H, m), 6.41 (2H, brs).

Provenance & Evidence