Ethyl Acetate → HCID 135732703, compound

HRID 407475Notes

Reaction equation

HRID 407475 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]([F:26])=[CH:22][C:21]=2[F:27])=[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:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[O:18])[CH:11]=[CH:12][C:13]=1[OH:14]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 9855836Potassium sodium tartarateHCID 11683556Nelotanserin2×

Product 1

HCID 135732703HCID 135732703, compoundYield 102.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea (Compound 8, 1.44 g, 3.30 mmol) was dissolved in anhydrous CH2Cl2 (30 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 (1.76 g, 13.20 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 then purified by HPLC, yielding 1.43 g (100%) of Compound 103 LCMS m/z (%)=425 (M+H81Br, 100), 423 (M+H79Br, 88). 1H NMR (400 MHz, DMSO-d6) δ 9.74 (s, 1H), 8.87 (s, 1H), 8.40 (s, 1H), 8.08-8.03 (m, 1H), 7.58 (s, 1H), 7.36 (dd, J1=8 Hz, J2=4 Hz, 1H), 7.33-7.27 (m, 1H), 7.28 (d, J=2 Hz, 1H), 7.04-7.01 (m, 1H), 6.95 (d, J=8 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 then purified by HPLC

Sources & evidence

ORD record
ord-d15f836902eb4965b9bc318768047434
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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