P-Anisidine → 3-(3-{3-t-Butyl-5-[3-(4-methoxy-phenyl)-ureido]-pyrazol-1-yl}-phenyl)-propionic acid ethyl ester

HRID 491997Notes

Reaction equation

HRID 491997 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.C1N=CN([C:15](N2C=NC=C2)=[O:16])C=1.[CH2:22]([O:24][C:25](=[O:44])[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([N:34]2[C:38]([NH2:39])=[CH:37][C:36]([C:40]([CH3:43])([CH3:42])[CH3:41])=[N:35]2)[CH:29]=1)[CH3:23]>CN(C=O)C>[CH2:22]([O:24][C:25](=[O:44])[CH2:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([N:34]2[C:38]([NH:39][C:15]([NH:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[O:16])=[CH:37][C:36]([C:40]([CH3:43])([CH3:42])[CH3:41])=[N:35]2)[CH:29]=1)[CH3:23]

Participants

5

Reactant 3

HCID 7732P-AnisidineHCID 682631,1'-CarbonyldiimidazoleHCID 58842892ethyl 3-(3-(3-t-butyl-5-amino-1H-pyrazol-1-yl)phenyl)propanoate

Product 1

HCID 588428573-(3-{3-t-Butyl-5-[3-(4-methoxy-phenyl)-ureido]-pyrazol-1-yl}-phenyl)-propionic acid ethyl esterYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 4-methoxy-phenylamine (123 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 a solution of Example Z (315 mg, 1.0 mmol) in DMF (2 mL). The resulting mixture was stirred at RT overnight then quenched with of 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), filtered, concentrated under reduced presume to yield a residue which was purified by flash chromatography to afford 3-(3-{3-t-butyl-5-[3-(4-methoxy-phenyl)-ureido]-pyrazol-1-yl}-phenyl)-propionic acid ethyl ester (210 mg, 45%). 1H-NMR (CD3OD): 7.46 (t, J=7.6 Hz, 1H), 7.38 (s, 1H), 7.34 (d, J=7.6 Hz, 2H), 7.24 (d, J=8.4 Hz, 2H), 6.84 (d, J=8.4 Hz, 2H), 6.38 (s, 1H), 4.09 (q, J=7.2 Hz, 2H), 3.75 (s, 3H), 3.00 (t, J=7.6 Hz, 2H), 2.68 (t, J=7.6 Hz, 2H), 1.33 (s, 9H), 1.20 (t, J=7.6 Hz, 3H); MS (ESI) m/z: 465 (M+H+).

Workup

  1. stirringThe resulting mixture was stirred at RT overnight
  2. customthen quenched with of water (50 mL)
  3. extractionThe reaction mixture was extracted with ethyl acetate (3×50 mL)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried (NaSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced presume
  8. customto yield a residue which
  9. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-9a21eaa05b3d4f13869b4f91718bf438
Source dataset
uspto-grants-2009_05
Patent number
US07531566B2

Reaction notes

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