Hydrochloric Acid → HCID 69057662, compound

HRID 734629Notes

Reaction equation

[ClH:1].[NH2:2][C:3]1[N:4](C(OC(C)(C)C)=O)[CH:5]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=3[F:31])=[O:19])=[CH:13][CH:12]=2)[C:7]=1[C:8](=[O:10])[NH2:9]>O1CCOCC1.CO>[ClH:1].[NH2:2][C:3]1[NH:4][CH:5]=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[CH:23][C:22]=3[F:31])=[O:19])=[CH:13][CH:12]=2)[C:7]=1[C:8](=[O:10])[NH2:9]

Participants

Conditions

Temperature: 50 °C

Procedure

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+).

Workup

concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record: ord-012fc9fd7e9d43e7b6ae8aea28f0b5d6
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592365B2

Reaction notes

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