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

HRID 1626181Notes

Reaction equation

HRID 1626181 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)=[O:17])[CH:10]=[CH:11][C:12]=2[O:13]C)=[CH:5][CH:4]=[N:3]1.ClC(Cl)C.BrB(Br)Br>O>[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([NH:15][C:16]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=3)=[O:17])[CH:10]=[CH:11][C:12]=2[OH:13])=[CH:5][CH:4]=[N:3]1

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 25134Boron tribromideHCID 117101541-(4-Chloro-phenyl)3-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

Product 1

HCID 1356979361-(4-Chloro-phenyl)-3-[4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 1-[3-(2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(4-chloro-phenyl)-urea (6.35 g, 17.8 mmol) and dichloroethane (500 mL), tribromoborane (10 mL, 106 mmol) was added. The mixture was allowed to warm to room temperature. After stirring over the weekend, the mixture was cooled in an ice bath and a mixture of ice cold ammonium hydroxide and water (ca. 100 mL) was added slowly. The mixture was transferred into a separatory funnel and extracted with methylene chloride and water. Solid in the water phase was filtered off and washed with water to give 1-[3-(2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea as a white solid (4.92 g, 90% pure, 12.7 mmol, 71%). Combined organic phases were dried over MgSO4, filtered, and concentrated to afford additional 1-[3-(2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(4-chloro-phenyl)-urea as a white solid (1.71 g, 4.99 mmol, 28%). Overall yield: 99%. LCMS m/z (%)=343.1 (M+H). 1H NMR (400 MHz, CDCl3) δ: 9.60 (br s, 1H), 8.78 (s, 1H), 8.53 (s, 1H), 7.48-7.42 (m, 3H), 7.32-7.27 (m, 4H), 6.91-6.89 (m, 1H), 6.21 (d, J=1.8 Hz, 1H), 3.68 (s, 3H).

Workup

  1. additionwas added
  2. temperaturethe mixture was cooled in an ice bath
  3. additionwas added slowly
  4. customThe mixture was transferred into a separatory funnel
  5. extractionextracted with methylene chloride and water
  6. filtrationSolid in the water phase was filtered off
  7. washwashed with water

Sources & evidence

ORD record
ord-6a08cee8437241c4a7a0964b79799d97
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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