Diisopropylethylamine → 3-{4-[4-(4-methanesulfonyl-piperazin-1-ylmethyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2263414Notes

Reaction equation

HRID 2263414 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][C:31]=1[C:32]1[NH:36][C:35](=[O:37])[O:34][N:33]=1)[O:6][CH2:7][C:8]1[S:12][C:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)=[N:10][C:9]=1[CH2:23]OS(C)(=O)=O.C(N(C(C)C)CC)(C)C.[CH3:47][S:48]([N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)(=[O:50])=[O:49]>CN(C)C=O>[CH3:47][S:48]([N:51]1[CH2:56][CH2:55][N:54]([CH2:23][C:9]2[N:10]=[C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][CH:14]=3)[S:12][C:8]=2[CH2:7][O:6][C:5]2[CH:29]=[CH:30][C:31]([C:32]3[NH:36][C:35](=[O:37])[O:34][N:33]=3)=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:53][CH2:52]1)(=[O:50])=[O:49]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7091611-(Methylsulfonyl)piperazineHCID 136149934HCID 136149934, compound

Product 1

HCID 1361499623-{4-[4-(4-methanesulfonyl-piperazin-1-ylmethyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-oneYield 11.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 50 mg of methanesulfonic acid 5-[3-methoxy-4-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenoxymethyl]-2-(4-trifluoromethyl-phenyl)-thiazol-4-ylmethyl ester in 2 mL of dimethylformamide was added 80 μL of diisopropylethyl amine and 19.2 mg of 1-methylsulfonylpiperazine. The resulting mixture was heated in a sealed tube to 90° C. under microwave irradiation for 5 minutes and then concentrated under reduced pressure. The residue was purified by chromatography on a SCX Waters column with gradient CH2Cl2/MeOH 30/70 to 7N NH3 in MeOH followed by recrystallization in dichloromethane 9/methanol 1 to give 6.7 mg of 3-{4-[4-(4-methanesulfonyl-piperazin-1-ylmethyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-methoxy-phenyl}-4H-[1,2,4]oxadiazol-5-one.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by chromatography on a SCX Waters column with gradient CH2Cl2/MeOH 30/70 to 7N NH3 in MeOH
  3. customfollowed by recrystallization in dichloromethane 9/methanol 1

Sources & evidence

ORD record
ord-3df338d3f27a48d68198dac0f6326f69
Source dataset
uspto-grants-2010_12
Patent number
US07851493B2

Reaction notes

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