Ethyl Acetate → 1-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-urea

HRID 407495Notes

Reaction equation

HRID 407495 reaction equation
[Cl: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.[Cl-].[Al+3].[Cl-].[Cl-].C(OCC)(=O)C>ClCCCl>[Cl: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

5

Reactant 3

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 116755501-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea2×

Product 1

HCID 1356979371-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-ureaYield 75%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea (Compound 77, example 1.61) (0.270 g, 0.69 mmol) in anhydrous 1,2-dichloroethane (10 mL) was cooled to 0° C. on an ice bath and stirred for 10 minutes. Anhydrous aluminium chloride (0.368 g, 2.76 mmol) was added and the reaction mixture stirred at 0° C. for 20 minutes, then moved to an oil bath and stirred at 80° C. for 1 hour. Ethyl acetate was added and washed with potassium sodium tartrate (10%) twice. Organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product that was further purified via HPLC. The corresponding fractions were collected and lyophilized to afford Compound 120 as a white solid in 75.0% yield. LCMS m/z (%)=379 (M+H 35Cl, 100), 381 (M+H 37Cl, 40). 1H NMR (400 MHz. DMSO-d6) δ: 9.81 (s, 1H), 8.92 (s, 1H), 8.45 (s, 1H), 8.12-8.06 (m, 1H), 7.63 (s, 1H), 7.40-7.31 (m, 3H), 7.09-7.04 (m, 1H), 6.99 (d, J1=8.72 Hz, 1H), 3.69 (s, 3H).

Workup

  1. stirringthe reaction mixture stirred at 0° C. for 20 minutes
  2. custommoved to an oil bath
  3. stirringstirred at 80° C. for 1 hour
  4. washwashed with potassium sodium tartrate (10%) twice
  5. customOrganic layer was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product that
  10. customwas further purified via HPLC
  11. customThe corresponding fractions were collected

Sources & evidence

ORD record
ord-403e2fc70ead464bae1d1af9924eb165
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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