Hydrochloric Acid → HCID 67213118, compound

HRID 227672Notes

Reaction equation

HRID 227672 reaction equation
C(OC([NH:8][C:9]1[C:10]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=3[F:37])=[O:25])=[CH:19][CH:18]=2)=[C:11]([C:14]([NH2:16])=[O:15])[NH:12][CH:13]=1)=O)(C)(C)C.[ClH:38]>O1CCOCC1.CCCCC>[ClH:38].[NH2:8][C:9]1[C:10]([C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[C:31]([C:33]([F:36])([F:34])[F:35])[CH:30]=[CH:29][C:28]=3[F:37])=[O:25])=[CH:19][CH:18]=2)=[C:11]([C:14]([NH2:16])=[O:15])[NH:12][CH:13]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57756893HCID 57756893, compound

Product 1

HCID 67213118HCID 67213118, compound

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
20 °C

Procedure

To 0.15 g (0.288 mmol) of 4-tert-butyloxycarbonylamino-3-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}-1H-pyrrole-2-carboxamide suspended in 1 cm3 of dioxane is added, at a temperature in the region of 20° C., 0.72 cm3 of a 4N solution of hydrogen chloride in dioxane. After stirring for 5 hours at a temperature in the region of 20° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give a residue, which is purified by flash chromatography [eluent: dichloromethane/methanol/acetonitrile (gradient of from 90/5/5 to 80/10/10 by volume)]. After concentrating the fractions under reduced pressure, 85 mg of a yellow solid are obtained, and are then stirred in 4 cm3 of pentane for 16 hours. After filtering through a No 3 sinter funnel, the solid is washed with twice 1 cm3 of pentane and then dried under reduced pressure (2.7 kPa) at a temperature in the region of 40° C. for 4 hours to give 47 mg of 4-amino-3-{4-[3-(2-fluoro-5-trifluoromethylphenyl)ureido]phenyl}-1H-pyrrole-2-carboxamide hydrochloride in the form of a yellow solid melting at about 174° C.; 1H NMR (400 MHz, DMSO d6, δ in ppm) from 5.30 to 8.00 (very broad m, 2H); 6.34 (d, J=2.5 Hz, 1H); 7.27 (d, J=8.5 Hz, 2H); 7.39 (m, 1H); 7.50 (partially masked m, 1H); 7.53 (d, J=8.5 Hz, 2H); 8.63 (broad d, J=7.0 Hz, 1H); 8.96 (broad s, 1H); 9.29 (s, 1H); 10.7 (broad s, 1H):; ES+: m/z=422: [M+H]+; ES−: m/z=420: [M−H]−.

Workup

  1. concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  2. customto give a residue, which
  3. customis purified by flash chromatography [eluent: dichloromethane/methanol/acetonitrile (gradient of from 90/5/5 to 80/10/10 by volume)]
  4. concentrationAfter concentrating the fractions under reduced pressure, 85 mg of a yellow solid
  5. customare obtained
  6. filtrationAfter filtering through a No 3 sinter funnel
  7. washthe solid is washed with twice 1 cm3 of pentane
  8. customdried under reduced pressure (2.7 kPa) at a temperature in the region of 40° C. for 4 hours

Sources & evidence

ORD record
ord-f63c65d473634a3bacc31e7e061615c6
Source dataset
uspto-grants-2009_07
Patent number
US07560571B2

Reaction notes

Loading…