4-Chlorobenzoic Acid → 3-{3-[3-t-Butyl-5-(4-chloro-benzoylamino)-pyrazol-1-yl]-phenyl}-propionic acid ethyl ester

HRID 1392314Notes

Reaction equation

HRID 1392314 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[CH2:11]([O:13][C:14](=[O:33])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([N:23]2[C:27]([NH2:28])=[CH:26][C:25]([C:29]([CH3:32])([CH3:31])[CH3:30])=[N:24]2)[CH:18]=1)[CH3:12]>O=S(Cl)Cl.C(Cl)Cl>[CH2:11]([O:13][C:14](=[O:33])[CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([N:23]2[C:27]([NH:28][C:6](=[O:8])[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)=[CH:26][C:25]([C:29]([CH3:32])([CH3:31])[CH3:30])=[N:24]2)[CH:18]=1)[CH3:12]

Participants

5

Reactant 2

HCID 63184-Chlorobenzoic AcidHCID 58842892ethyl 3-(3-(3-t-butyl-5-amino-1H-pyrazol-1-yl)phenyl)propanoate

Product 1

HCID 588428933-{3-[3-t-Butyl-5-(4-chloro-benzoylamino)-pyrazol-1-yl]-phenyl}-propionic acid ethyl esterYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 4-chlorobenzoic acid (312 mg, 2.0 mmol) in SOCl2 (10 mL) was heated to reflux for 2 h. After removal of the solvent, the residue was dissolved into CH2Cl2 (5 mL) and was dropped into a solution of Example Z (315 mg, 1.0 mmol) in CH2Cl2 (10 mL) at 0° C., was then stirred at RT overnight. After quenching with water (50 mL), the reaction mixture was extracted with CH2Cl2 (3×100 mL). 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-(4-chloro-benzoylamino)-pyrazol-1-yl]-phenyl}-propionic acid ethyl ester (290 mg, 64%). 1H-NMR (CDCL3): 8.02 (s, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.46 (t, J=7.6 Hz, 1H), 7.44 (d, J=8.4 Hz, 2H), 7.36 (t, J=8.4 Hz, 3H), 6.87 (s, 1H), 4.06 (q, J=7.6 Hz, 2H), 3.02 (t, J=7.6 Hz, 2H), 2.67 (t, J=7.6 Hz, 2H), 1.40 (s, 9H), 1.12 (t, J=7.6 Hz, 3H); MS (ESI) m/z: 454 (M+H+).

Workup

  1. temperatureto reflux for 2 h
  2. customAfter removal of the solvent
  3. dissolutionthe residue was dissolved into CH2Cl2 (5 mL)
  4. customAfter quenching with water (50 mL)
  5. extractionthe reaction mixture was extracted with CH2Cl2 (3×100 mL)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (NaSO4)
  8. filtrationfiltered
  9. concentrationAfter concentrated under reduced pressure
  10. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-d05caafc59c147989362b07c98b73f95
Source dataset
uspto-grants-2008_03
Patent number
US07342037B2

Reaction notes

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