Cesium carbonate → HCID 67528381, compound

HRID 2261859Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([NH:22][CH3:23])=[C:18]([CH3:24])[CH:17]=2)=[C:12]([CH:25]([CH3:27])[CH3:26])[CH:11]=[N:10]1.[CH3:28][O:29][C:30](=[O:40])[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38]Br)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH3:28][O:29][C:30](=[O:40])[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([CH2:38][N:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH2:14][C:13]3[N:9]([C:3]4[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[N:10]=[CH:11][C:12]=3[CH:25]([CH3:27])[CH3:26])=[CH:17][C:18]=2[CH3:24])[CH3:23])=[CH:34][CH:33]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To an ambient temperature solution of {4-[2-(2,6-dichloro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethoxy]-2-methyl-phenyl}-methyl-amine (82 mg, 0.204 mmol) in acetonitrile (3 mL) are added (4-bromomethyl-phenyl)-acetic acid methyl ester (52 mg, 0.214 mmol) and cesium carbonate (133 mg, 0.408 mmol). The reaction mixture is heated to 80° C. overnight. The reaction mixture is concentrated under reduced pressure. The residue is chromatographed (SiO2 40 g, 0% to 20% EtOAc/Hex). Reversed phase HPLC (C18 OBD 19×100 mm, 30 to 70% ACN/water (0.1% TFA) at 20 mL/min) is employed to remove approximately 10% starting amine present to yield the title compound (78 mg, 68%). LC-ES/MS m/e 566.3 (M+1), 95%

Workup

concentrationThe reaction mixture is concentrated under reduced pressure
customThe residue is chromatographed (SiO2 40 g, 0% to 20% EtOAc/Hex)
customto remove approximately 10%

Sources & evidence

ORD record: ord-da46883afa424a0e971fb759f75adf2b
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07846960B2

Reaction notes

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