Benzene, 1-chloro-3-isocyanato- → 1-(3-Chloro-phenyl)-3-[3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-urea

HRID 540552Notes

Reaction equation

HRID 540552 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:19]=[C:20]([N:24]=[C:25]=[O:26])[CH:21]=[CH:22][CH:23]=1>>[Cl:17][C:18]1[CH:19]=[C:20]([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:21]=[CH:22][CH:23]=1

Participants

3

Reactant 2

HCID 17968Benzene, 1-chloro-3-isocyanato-HCID 231394493-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine

Product 1

HCID 115016721-(3-Chloro-phenyl)-3-[3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-ureaYield 27%

Procedure

3-(4-Fluoro-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine was treated with 3-chlorophenylisocyanate, in a similar manner as described in Example 1.68. An additional purification by flash chromatography (SiO2, Hexanes/EtOAc gradient elution) was necessary, providing a 10 mg (27% yield) of Compound 83: LCMS m/z (%)=377 (M+H37Cl, 25), 375 (M+H35Cl, 100). 1H NMR (400 MHz, acetone-d6) δ: 8.28 (s, 1H), 8.16 (s, 1H), 7.80 (s, 1H), 7.64 (dd, J1=8.8 Hz, J2=2.8 Hz, 1H), 7.48 (d, J=2.8 Hz, 1H), 7.38 (d, JH,F=4.8 Hz, 1H), 7.34 (dd, J1=9.2 Hz, J2=0.8 Hz, 1H), 7.26 (dd, J1=8.2, J2=8.2 Hz, 1H), 7.13 (d, J=8.8 Hz, 1H), 7.00 (dd, J1=8.8 Hz, J2=0.8 Hz, 1H), 3.83 (s, 3H), 3.65 (s, 3H). 19F NMR (376 MHz, acetone-d6) δ: −177.35 (d, JH,F=4.1 Hz, 1F).

Workup

  1. customAn additional purification
  2. washby flash chromatography (SiO2, Hexanes/EtOAc gradient elution)

Sources & evidence

ORD record
ord-be16bf4ff32b4d46a98d8f83f7621d15
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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