Ethyl Acetate → 1-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)urea

HRID 919508Notes

Reaction equation

HRID 919508 reaction equation
[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:16][C:17]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)=[O:18])[CH:11]=[CH:12][C:13]=1[O:14]C.[Al+3].[Cl-].[Cl-].[Cl-].CCOC(C)=O.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>C(Cl)Cl>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:16][C:17]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=2)=[O:18])[CH:11]=[CH:12][C:13]=1[OH:14]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 9855836Potassium sodium tartarateHCID 112475691-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-Chloro-phenyl)-urea

Product 1

HCID 1355074951-(3-(4-bromo-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-3-(4-chlorophenyl)ureaYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Compound 1, (1.56 g, 3.58 mmol) was dissolved in anhydrous CH2Cl2 (50 mL). The solution was stirred while cooling the temperature to 0° C. in an ice water bath. After allowing it to stir for another 10 minutes, AlCl3 (1.91 g, 14.32 mmol) was added slowly. This was followed by stirring the reaction for an additional 20 minutes, and subsequently increasing the temperature to 80° C. After one hour, the reaction was shown to be complete by TLC and LC/MS. It was worked up with EtOAc (2×50 mL) and 10% Potassium Sodium Tartrate (2×50 mL). Upon being treated to this work up, the aluminum was removed from the solution. The organic layer was then dried with Na2SO4, filtered, and the solvent was removed under reduced pressure. The residue was purified by HPLC to afford Compound 58 (402 mg, 27%): LCMS m/z (%)=423 (M+H37Cl, 100), 421 (M+H35Cl, 98). 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.76 (s, 1H), 8.59 (s, 1H), 7.60 (s, 1H), 7.48 (d, J=8 Hz, 2H), 7.39 (dd, J1=8 Hz, J2=4 Hz, 1H), 7.32 (d, J=8 Hz, 2H), 7.28 (d, J=2 Hz, 1H), 6.96 (d, J=12 Hz, 1H), 3.67 (s, 3H).

Workup

  1. stirringto stir for another 10 minutes
  2. stirringby stirring
  3. customthe reaction for an additional 20 minutes
  4. temperaturesubsequently increasing the temperature to 80° C
  5. additionUpon being treated to this work up
  6. customthe aluminum was removed from the solution
  7. dry with materialThe organic layer was then dried with Na2SO4
  8. filtrationfiltered
  9. customthe solvent was removed under reduced pressure
  10. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-36c31576d0674ab3b6bfc7b4884a7647
Source dataset
uspto-grants-2016_03
Patent number
US09273035B2

Reaction notes

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