Water → 3-(3-{3-t-Butyl5-[3-(4-fluoro-phenyl)-ureido]-pyrazol-1-yl}-phenyl)-propionic acid ethyl ester

HRID 491995

Reaction equation

HRID 491995 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][CH:3]=1.C1N=CN([C:14](N2C=NC=C2)=[O:15])C=1.[CH2:21]([O:23][C:24](=[O:43])[CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([N:33]2[C:37]([NH2:38])=[CH:36][C:35]([C:39]([CH3:42])([CH3:41])[CH3:40])=[N:34]2)[CH:28]=1)[CH3:22].O>CN(C=O)C>[CH2:21]([O:23][C:24](=[O:43])[CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([N:33]2[C:37]([NH:38][C:14]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[O:15])=[CH:36][C:35]([C:39]([CH3:42])([CH3:41])[CH3:40])=[N:34]2)[CH:28]=1)[CH3:22]

Participants

6

Reactant 4

HCID 962WaterHCID 97314-FluoroanilineHCID 682631,1'-CarbonyldiimidazoleHCID 58842892ethyl 3-(3-(3-t-butyl-5-amino-1H-pyrazol-1-yl)phenyl)propanoate

Product 1

HCID 588428503-(3-{3-t-Butyl5-[3-(4-fluoro-phenyl)-ureido]-pyrazol-1-yl}-phenyl)-propionic acid ethyl esterYield 33.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 4-fluoro-phenylamine (111 mg, 1.0 mmol) and CDI (165 mg, 1.0 mmol) in DMF (2 mL) was stirred at RT for 30 min, and was then added to a solution of Example Z (315 mg, 1.0 mmol) in DMF (2 mL). The resulting mixture was stirred at RT overnight then added to water (50 mL). The reaction mixture was extracted with ethyl acetate (3×50 mL) and the combined organic extracts were washed with brine, dried (NaSO4) and filtered. After concentrated under reduced pressure, the residue was purified by flash chromatography to afford 3-(3-{3-t-butyl-5-[3-(4-fluoro-phenyl)-ureido]-pyrazol-1-yl}-phenyl)-propionic acid ethyl ester (150 mg, 33%). 1H-NMR (CDCl3): 7.91 (s, 1H), 7.42 (d, J=4.8 Hz, 1H), 7.37-7.34 (m, 2H), 7.28 (s, 1H), 7.17-7.16 (m, 2H), 6.98 (t, J=8.8 Hz, 2H), 6.59 (s, 1H), 4.04 (q, J=7.2 Hz, 2H), 3.03 (t, J=7.2 Hz, 2H), 2.77 (t, J=7.2 Hz, 2H), 1.36 (s, 9H), 1.17 (t, J=7.2 Hz, 3H); MS (ESI) m/z: 453 (M+H+).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate (3×50 mL)
  2. washthe combined organic extracts were washed with brine
  3. dry with materialdried (NaSO4)
  4. filtrationfiltered
  5. concentrationAfter concentrated under reduced pressure
  6. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-ba5911e4bc59464b9a2faab7173a5a1f
Source dataset
uspto-grants-2009_05
Patent number
US07531566B2

Linked notes

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