N-bromobutanimide → 1-[3-(4-Bromo-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-urea

HRID 407515Notes

Reaction equation

HRID 407515 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([C:21]2[NH:22][N:23]=[CH:24][CH:25]=2)[CH:14]=1)=[O:11].[Br:26]N1C(=O)CCC1=O.C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>CN(C=O)C>[Br:26][C:25]1[CH:24]=[N:23][NH:22][C:21]=1[C:15]1[CH:14]=[C:13]([NH:12][C:10]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[O:11])[CH:18]=[CH:17][C:16]=1[O:19][CH3:20]

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 22607107sodium thiosulfate NaHCO3HCID 231394671-(2,4-Difluoro-phenyl)-3-[4-methoxy-3-(2H-pyrazol-3-yl)-phenyl]-urea

Product 1

HCID 231395161-[3-(4-Bromo-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)-ureaYield 92.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cooled and stirred solution of 1-(2,4-Difluoro-phenyl)-3-[4-methoxy-3-(2H-pyrazol-3-yl)-phenyl]-urea (0.6 g, 1.74 mmole) in DMF (15 mL) was added N-bromosuccinimide (0.37 g, 2.09 mmole) over a period of 15 minutes. The reaction mixture was warmed slowly to ambient temperature and stirred for another 2 hrs. The reaction mixture was poured into well-stirred ice water containing NaHCO3/Na2S2O3. The resulting solid was filtered and washed with ice water (50 mL). The solid was dried in vacuo to afford off-white solid (0.68 g, 92%). LCMS m/z (%)=425 (M+H, 79Br, 100), 427 (M+H, 81 Br, 99). 1H NMR (Bruker, 400 MHz, DMSO-d6) δ: 8.96 (bs, 1H), 8.44 (bs, 1H), 8.02-8.08 (m, 1H), 7.48 (bs, 2H), 7.27-7.32 (m, 1 h), 6.99-7.08 (m, 2H), 3.73 (s, 3H) (major tautomer).

Workup

  1. temperatureTo a cooled
  2. additionThe reaction mixture was poured
  3. filtrationThe resulting solid was filtered
  4. washwashed with ice water (50 mL)
  5. customThe solid was dried in vacuo

Sources & evidence

ORD record
ord-6dc3edadd95e4afda40da783e86c2486
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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