4-Chlorophenyl Isocyanate → 1-(4-Chloro-phenyl)-3-[3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-urea

HRID 407431Notes

Reaction equation

HRID 407431 reaction equation
[F:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH2:16])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]=[C:25]=[O:26])=[CH:20][CH:19]=1>C(Cl)Cl>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][C:25]([NH:16][C:10]2[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:8]([C:3]3[N:4]([CH3:7])[N:5]=[CH:6][C:2]=3[F:1])[CH:9]=2)=[O:26])=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 76934-Chlorophenyl IsocyanateHCID 231394493-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine

Product 1

HCID 115380391-(4-Chloro-phenyl)-3-[3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-ureaYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(4-Fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine (49 mg, 0.22 mmol) was dissolved in 3 mL of CH2Cl2, treated with 4-chlorophenylisocyanate (40 mg, 0.27 mmol), and stirred at room temperature overnight. The solvent was removed under reduced pressure, dissolved in DMSO (5 ml), and purified by preparative HPLC to afford Compound 27 as a white solid, 41 mg, 49% yield: LCMS m/z (%)=377 (M+H37Cl, 31), 375 (M+H35Cl, 100). 1H NMR (400 MHz, acetone-d6) δ: 8.77 (s, 1H), 8.67 (s, 1H), 7.66 (ddd, J1=9.0 Hz, J2=2.6 Hz, 1H), 7.60 (d, J=9.2 Hz, 2H), 7.54 (d, J=2.8 Hz, 1H), 7.38 (d, JH,F=4.4 Hz, 1H), 7.27 (d, J=8.8 Hz, 2H), 7.12 (d, J=8.8 Hz, 1H), 3.83 (s, 3H), 3.65 (s, 3H). 19F NMR (376 MHz, acetone-d6) δ: −177.39 (d, JH,F=5.3 Hz, 1F).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutiondissolved in DMSO (5 ml)
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-15b41eaed52e496b9665cfde63bf333b
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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