2,4-Difluorophenyl isocyanate → HCID 11690689, compound

HRID 1626224Notes

Reaction equation

HRID 1626224 reaction equation
[N:1]1([CH2:6][CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=2[C:16]2[N:17]([CH3:21])[N:18]=[CH:19][CH:20]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[N:30]=[C:31]=[O:32]>ClCCl>[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[NH:30][C:31]([NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[C:10]([C:16]2[N:17]([CH3:21])[N:18]=[CH:19][CH:20]=2)[CH:11]=1)=[O:32]

Participants

4

Reactant 2

HCID 5932582,4-Difluorophenyl isocyanateHCID 58243071HCID 58243071, compound

Product 1

HCID 11690689HCID 11690689, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-imidazol-1-yl-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine (0.08 g, 0.256 mmol) in 2.0 mL of dichloromethane was added 2,4-difluoro phenyl isocyanate (0.042 g, 0.280 mmol), and the mixture was stirred at ambient temperature overnight. The DCM was evaporated from the reaction mixture, the crude residue was dissolved in 5.0 mL of DMSO and purified by RP-HPLC. The proper fractions were collected and lyophilized to afford the 1-(2,4-difluoro-phenyl)-3-[4-(2-imidazol-1-yl-ethoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea as an off-white solid in 75% yield. LCMS m/z (%)=439 (M+H). 1H NMR (400 MHz, Acetone-d6) δ: 8.46 (bs, 1H), 7.96-8.02 (m, 1H), 7.48 (dd, J=8.9 and 2.72 Hz, 1H), 7.39-7.41 (m, 2H), 7.31 (d, J=1.81 Hz, 1H), 7.17 (t, J=1.42 Hz, 1H), 6.94 (d, J=8.94 Hz, 1H), 6.7-6.8 (m, 2H), 6.01 (d, J=1.78 Hz, 1H), 4.62 (t, J=4.74 Hz, 2H), 4.33 (t, J=5.07 Hz, 2H), 3.48 (s, 3H).

Workup

  1. customThe DCM was evaporated from the reaction mixture
  2. dissolutionthe crude residue was dissolved in 5.0 mL of DMSO
  3. custompurified by RP-HPLC
  4. customThe proper fractions were collected

Sources & evidence

ORD record
ord-319863101cf747418938e1e38ed20105
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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