Tetrahydrofuran → (2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-cyclohexyl-1H-benzo[d]imidazol-5-yl)methanol

Participants

Reaction Steps

In a 20 mL microwave reaction tube was weighed 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (653 mg, 0.00144 mol). To this was added (2-amino-1-cyclohexyl-1H-benzoimidazol-5-yl)methanol (322.1 mg, 0.001313 mol), trans-N1,N2-dimethylcyclohexane-1,2-diamine (121 mg, 0.000851 mol), copper(I) iodide (78 mg, 0.00041 mol) and potassium phosphate (554 mg, 0.00261 mol). The tube was purged with argon and tetrahydrofuran (14 mL, 0.17 mol) was then added. The reaction mixture was stirred for several minutes with argon sparging at room temp. The reaction mixture was then heated under microwave irradiation for 5 hours at 140° C. The reaction mixture was cooled and diluted with ethyl acetate and washed twice with aqueous sodium bicarbonate, once with dilute HCl and one final wash with dilute sodium bicarbonate. The organic phase was dried over sodium sulfate and concentrated. The residue (750 mg) was purified by flash chromatography using a 120 g silica gel cartridge and hexane and ethyl acetate eluent. The product was loaded onto the column with methylene chloride and the eluent was initially 10% ethyl acetate for 2 minutes then a gradient to 60% ethyl acetate over 20 mins. The product fractions were combined and concentrated to yield 334.6 mg of a pale greenish white solid.

Provenance & Evidence