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

HRID 919462Notes

Reaction equation

HRID 919462 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-f128b802a0694690a2e7fd0cc554b06e
Source dataset
uspto-grants-2016_03
Patent number
US09273035B2

Reaction notes

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