Trimethylaluminum → 3-[[1-(4-Fluorophenyl)-5-isopropylpyrazol-4-yl]amino]-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propan-1-ol

HRID 522317Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH:13]([CH3:15])[CH3:14])=[C:11]([NH2:16])[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:17][C:18]1[N:19]([CH:27]2[CH2:31][CH2:30][O:29]C2=O)[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=1.C[Al](C)C>[OH-].[NH4+]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([CH:13]([CH3:14])[CH3:15])=[C:11]([NH:16][CH:27]([N:19]3[CH:20]=[C:21]([C:23]([F:25])([F:26])[F:24])[N:22]=[C:18]3[CH3:17])[CH2:31][CH2:30][OH:29])[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 55 °C

Procedure

A mixture of 1-(4-fluorophenyl)-5-isopropyl-pyrazol-4-amine (0.070 g, 0.32 mmol), 3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]tetrahydrofuran-2-one (0.070 g, 0.30 mmol) and AlMe3 (0.50 mL, 1.0 mmol, 2 M/toluene) was heated at 55° C. for 1.5 hrs. The mixture was then cooled to room temperature, diluted with aqueous ammonium hydroxide, and extracted with EtOAc. The organic layer was separated, dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography (SiO2, 0˜20% MeOH/CH2Cl2 gradient elution) to give 3-[[1-(4-fluorophenyl)-5-isopropylpyrazol-4-yl]amino]-3-[2-methyl-4-(trifluoromethyl)imidazol-1-yl]propan-1-ol (0.030 g, 24%).

Workup

temperatureThe mixture was then cooled to room temperature
extractionextracted with EtOAc
customThe organic layer was separated
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated in vacuo
custompurified by flash chromatography (SiO2, 0˜20% MeOH/CH2Cl2 gradient elution)

Sources & evidence

ORD record: ord-d3fe0f7fe50147b5bbd43efbdbda4cba
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328116B2

Reaction notes

Loading…