Thiophene-3-boronic acid → HCID 56932370, compound
Reaction equation
[S:1]1[CH:5]=[CH:4][C:3](B(O)O)=[CH:2]1.Br[C:10]1[CH:11]=[C:12]([C:30]([OH:39])([C:35]([F:38])([F:37])[F:36])[C:31]([F:34])([F:33])[F:32])[CH:13]=[CH:14][C:15]=1[N:16]1[CH2:21][CH2:20][N:19]([S:22]([C:25]2[S:26][CH:27]=[CH:28][CH:29]=2)(=[O:24])=[O:23])[CH2:18][CH2:17]1>>[F:32][C:31]([F:34])([F:33])[C:30]([C:12]1[CH:13]=[CH:14][C:15]([N:16]2[CH2:21][CH2:20][N:19]([S:22]([C:25]3[S:26][CH:27]=[CH:28][CH:29]=3)(=[O:24])=[O:23])[CH2:18][CH2:17]2)=[C:10]([C:3]2[CH:4]=[CH:5][S:1][CH:2]=2)[CH:11]=1)([OH:39])[C:35]([F:38])([F:37])[F:36]Participants
Procedure
Following the procedure outlined for Example 69, 3-thiopheneboronic acid (17.8 mg, 0.139 mmol, Sigma-Aldrich, St. Louis, Mo.) was coupled to 2-(3-bromo-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol, the reaction mixture was filtered, concentrated, and the residue was subjected to reverse-phase preparative HPLC using a Phenomenex Gemini-NX (C18 110 A column (100×21 mm, 5 μm) eluting with 0.1% NH4OH in CH3CN/H2O (5% to 95% over 8 min)) to afford 1,1,1,3,3,3-hexafluoro-2-(3-(3-thiophenyl)-4-(4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol. 1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J=6.2 Hz, 1H), 7.69-7.62 (m, 2H), 7.53 (m, 3H), 7.38-7.29 (m, 2H), 7.19 (d, J=9.7 Hz, 1H), 2.99-2.94 (m, 4H), 2.93-2.87 (m, 4H). m/z (ESI, +ve ion) 557.0 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=3.50 μM; GK-GKRP EC50 (LC MS/MS)=1.90 μM.
Workup
- filtrationthe reaction mixture was filtered
- concentrationconcentrated
- washa Phenomenex Gemini-NX (C18 110 A column (100×21 mm, 5 μm) eluting with 0.1% NH4OH in CH3CN/H2O (5% to 95% over 8 min))
Sources & evidence
- ORD record
- ord-b474a61ae2f04426a25867bcf75dc40b
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431563B2
Reaction notes
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