Triethylamine → 2-[4-[(3R)-3-Methyl-4-(2-thienylsulfonyl)piperazino]phenyl]-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972372Notes

Reaction equation

HRID 1972372 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][NH:18][C@H:17]([CH3:21])[CH2:16]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[S:29](Cl)(=[O:31])=[O:30].C(N(CC)CC)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:23][C:2]([F:1])([F:22])[C:3]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:29]([C:25]3[S:24][CH:28]=[CH:27][CH:26]=3)(=[O:31])=[O:30])[C@H:17]([CH3:21])[CH2:16]2)=[CH:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 855182-Thiophenesulfonyl chlorideHCID 86670311HCID 86670311, compound

Product 1

HCID 763364292-[4-[(3R)-3-Methyl-4-(2-thienylsulfonyl)piperazino]phenyl]-1,1,1,3,3,3-hexafluoro-2-propanolYield 31.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A 100 mL round-bottomed flask was charged with 1,1,1,3,3,3-hexafluoro-2-(4-((3R)-3-methyl-1-piperazinyl)phenyl)-2-propanol (0.950 g, 2.78 mmol), 5 mL of CH2Cl2, 2-thiophenesulfonyl chloride (0.583 g, 3.19 mmol, Sigma-Aldrich, St. Louis, Mo.), and triethylamine (0.580 mL, 4.16 mmol). After 1 h at room temperature, 0.010 g of DMAP was added. After an additional 30 min, the mixture was concentrated and purified via column chromatography (80 g of silica, 0 to 40% EtOAc in hexanes) to give 1,1,1,3,3,3-hexafluoro-2-(4-((3R)-3-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol (0.425 g) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ=7.70-7.46 (m, 4H), 7.12 (dd, J=3.7, 4.9 Hz, 1H), 6.94 (d, J=9.0 Hz, 2H), 4.30 (m, 1H), 3.83 (td, J=3.0, 13.1 Hz, 1H), 3.66-3.57 (m, 1H), 3.54-3.38 (m, 2H), 3.31 (s, 1H), 3.07 (dd, J=3.5, 12.3 Hz, 1H), 2.95 (dt, J=3.6, 11.6 Hz, 1H), 1.30 (d, J=6.7 Hz, 3H). m/z (ESI, +ve ion) 488.7 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=2.36 μM; GK-GKRP EC50 (LC MS/MS)=2.57 μM.

Workup

  1. waitAfter an additional 30 min
  2. concentrationthe mixture was concentrated
  3. custompurified via column chromatography (80 g of silica, 0 to 40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-475bc78d550a41bab38a1aef65c233dc
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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