Hydrochloric Acid → HCID 69057662, compound

Participants

Reaction Conditions

Reaction Steps

0.575 cm3 of a 4M hydrochloric acid solution in dioxane is added at a temperature in the region of 20° C., under an argon atmosphere, to 0.06 g (0.115 mmol) of tert-butyl 2-amino-3-carbamoyl-4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}pyrrole-1-carboxylate in solution in a mixture of 1.2 cm3 of dioxane and 1.2 cm3 of methanol. After stirring for 15 hours at a temperature in the region of 50° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give 2-amino-3-carbamoyl-4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}-1H-pyrrole hydrochloride which is taken up in 2.5 cm3 of ethyl acetate. 0.01 cm3 of triethylamine and 0.013 cm3 of acetic anhydride are added at a temperature in the region of 20° C., under an argon atmosphere. After stirring for 1 hour at a temperature in the region of 20° C., a catalytic quantity of DMAP is added and then the stirring is maintained for 30 minutes. The reaction mixture is diluted with 5 cm3 of ethyl acetate. The organic phase is washed with twice 5 cm3 of water. All the aqueous phases are combined and extracted with 5 cm3 of ethyl acetate. All the organic phases are combined, washed with 5 cm3 of a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (2.7 kPa) to give 0.054 g of a residue which is purified by flash chromatography [eluent: dichloromethane/methanol (98/2 by volume)]. After concentrating the fractions under reduced pressure, 0.010 g of 1-acetyl-2-amino-4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}-1H-pyrrole-3-carboxamide is obtained, in the form of a yellow solid; 1H NMR (300 MHz, (CD3)2SO, —δ in ppm): 2.14 (s: 3H); from 5.20 to 6.10 (broad m: 1H); 6.40 (d, J=2.0 Hz: 1H); from 6.70 to 7.60 (broad m: 1H); 7.30 (broad d, J=8.5 Hz: 2H); 7.38 (mt: 1H); from 7.45 to 7.54 (m: 3H); 8.62 (dd, J=7.5 and 2.5 Hz: 1H); 8.92 (broad s: 1H); 9.25 (broad s: 1H); 10.7 (broad s: 1H); 11.4 (broad s: 1H); ES+: m/z=464 (MH+).

Provenance & Evidence