Diisopropylethylamine → HCID 76314690, compound

HRID 1972427Notes

Reaction equation

HRID 1972427 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6](Cl)(=[O:8])=[O:7].Cl.[CH2:11]([C@H:13]1[CH2:18][NH:17][CH2:16][CH2:15][N:14]1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([OH:34])([C:30]([F:33])([F:32])[F:31])[C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=1)[CH3:12].CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:11]([C@H:13]1[CH2:18][N:17]([S:6]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)(=[O:8])=[O:7])[CH2:16][CH2:15][N:14]1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([OH:34])([C:26]([F:28])([F:29])[F:27])[C:30]([F:31])([F:32])[F:33])=[CH:21][CH:20]=1)[CH3:12]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 855182-Thiophenesulfonyl chlorideHCID 86670327HCID 86670327, compound

Product 1

HCID 76314690HCID 76314690, compoundYield 17.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Thiophenesulfonyl chloride (0.28 g, 1.5 mmol, Sigma-Aldrich, St. Louis, Mo.) was added to a stirring solution of 2-(4-((2S)-2-ethyl-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol hydrochloride (0.55 g, 1.5 mmol), Hünig's base (0.81 mL, 4.6 mmol), and DMF (7.7 mL) at room temperature. After 19 h, the reaction mixture was partitioned between EtOAc (20 mL) and saturated aqueous sodium bicarbonate (10 mL). The layers were separated, and the organic material was washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried (Na2SO4) and purified via column chromatography (40 g of silica, 20 to 33% EtOAc in hexanes) to give 2-(4-((2S)-2-ethyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.13 g) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 7.63 (d, J=5.1 Hz, 1H), 7.59-7.49 (m, 3H), 7.19-7.13 (m, 1H), 6.83 (d, J=8.0 Hz, 2H), 3.77 (d, J=11.0 Hz, 3H), 3.49 (d, J=12.7 Hz, 1H), 3.32 (dt, J=3.1, 11.9 Hz, 1H), 3.24 (s, 1H), 2.74-2.51 (m, 2H), 1.89 (ddd, J=7.3, 9.3, 14.0 Hz, 1H), 1.60-1.47 (m, 1H), 0.94 (t, J=7.4 Hz, 3H); m/z (ESI, +ve ion) 503.0 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=0.679 μM; GK-GKRP EC50 (LC MS/MS)=1.37 μM.

Workup

  1. customthe reaction mixture was partitioned between EtOAc (20 mL) and saturated aqueous sodium bicarbonate (10 mL)
  2. customThe layers were separated
  3. washthe organic material was washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. custompurified via column chromatography (40 g of silica, 20 to 33% EtOAc in hexanes)

Sources & evidence

ORD record
ord-edea437eda5b4ec9a59c6ae8f88925b4
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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