Dimethyl Sulfoxide → 8-(6-(4-(1-(4-Fluorophenyl)ethyl)piperazin-1-yl)pyrimidin-4-yloxy)isoquinoline

HRID 1787450Notes

Reaction equation

F[C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH3:15])[CH2:10][CH2:9]2)[N:5]=[CH:4][N:3]=1.[CH:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][C:31]=2[OH:33])[CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(C)=O>O>[F:22][C:19]1[CH:20]=[CH:21][C:16]([CH:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]3[N:5]=[CH:4][N:3]=[C:2]([O:33][C:31]4[CH:30]=[CH:29][CH:28]=[C:27]5[C:32]=4[CH:23]=[N:24][CH:25]=[CH:26]5)[CH:7]=3)[CH2:9][CH2:10]2)[CH3:15])=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 115 °C

Procedure

A mixture of 4-fluoro-6-(4-(1-(4-fluorophenyl)ethyl)piperazin-1-yl)pyrimidine, Example 33(a), (0.05 g, 0.17 mmol), isoquinolin-8-ol (0.037 g, 0.25 mmol, Monomer Chem, Inc.) cesium carbonate (0.081 g, 0.25 mmol), and DMSO (1 mL) was heated in a microwave synthesizer at 115° C. for 0.5 h. The reaction mixture was allowed to cool to room temperature, diluted with H2O (30 mL) and extracted with DCM (2×50 mL). The combined organic extracts were washed with H2O (2×30 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (gradient: 0-8% MeOH/DCM) to give the title compound as a white solid. Mp: 114° C. MS (ESI, pos. ion) m/z: 430 (M+1).

Workup

temperatureto cool to room temperature
extractionextracted with DCM (2×50 mL)
washThe combined organic extracts were washed with H2O (2×30 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography (gradient: 0-8% MeOH/DCM)

Sources & evidence

ORD record: ord-3fb9432be33a41eea3da2dbde4229451
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07511044B2

Reaction notes

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