4-Hydroxyphenylboronic acid → HCID 86670334, compound

HRID 1972443Notes

Reaction equation

HRID 1972443 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.Br[C:12]1[CH:13]=[C:14]([C:32]([OH:41])([C:37]([F:40])([F:39])[F:38])[C:33]([F:36])([F:35])[F:34])[CH:15]=[CH:16][C:17]=1N1CCN(S(C2SC=CC=2)(=O)=O)CC1>>[F:34][C:33]([F:35])([F:36])[C:32]([C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)[CH:13]=1)([OH:41])[C:37]([F:38])([F:40])[F:39]

Participants

3

Reactant 2

HCID 27343604-Hydroxyphenylboronic acidHCID 86670331HCID 86670331, compound

Product 1

HCID 86670334HCID 86670334, compound

Procedure

Following the procedure outlined for Example 69, 4-hydroxyphenylboronic acid (19.2 mg, 0.139 mmol) 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 2′44-(2-thiophenylsulfonyl)-1-piperazinyl)-5′-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-4-biphenylol. 1H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J=5.3 Hz, 1H), 7.65 (d, J=4.0 Hz, 1H), 7.53-7.46 (m, 1H), 7.38 (s, 1H), 7.36-7.25 (m, 3H), 7.13 (d, J=8.8 Hz, 1H), 6.72 (d, J=8.8 Hz, 2H), 2.89 (br. s, 8H). m/z (ESI, +ve ion) 567.0 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=1.47 μM; GK-GKRP EC50 (LC MS/MS)=1.37 μM.

Workup

  1. filtrationthe reaction mixture was filtered
  2. concentrationconcentrated
  3. 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-88dafdeb24304f138171c2b4b0d2b737
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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