Diisopropylethylamine → HCID 56932988, compound

HRID 1972386Notes

Reaction equation

HRID 1972386 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].[S:23]1[CH:27]=[CH:26][N:25]=[C:24]1[S:28](Cl)(=[O:30])=[O:29].CCN(C(C)C)C(C)C>C(Cl)Cl>[F:5][C:4]([F:7])([F:6])[C:3]([OH:8])=[O:29].[F:22][C:2]([F:1])([F:21])[C:3]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:28]([C:24]3[S:23][CH:27]=[CH:26][N:25]=3)(=[O:30])=[O:29])[CH2:17][CH2:16]2)=[CH:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 115792352-Thiazolesulfonyl chlorideHCID 866237611,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol

Product 1

HCID 56932988HCID 56932988, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol (150 mg, 0.457 mmol, published PCT patent application no. WO 2006/094842) was suspended in 20 mL of CH2Cl2. To this was added 2-thiazolesulfonyl chloride (84 mg, 0.457 mmol, Bioorg. Med. Chem., 2006, 14, 6628) and Hünig's base (0.2 mL). After stirring for 20 min at room temperature, the reaction was concentrated and then re-dissolved in methanol (3 mL). The crude material was purified by reverse-phase preparative HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), eluting with a 0.1% TFA in CH3CN/H2O, gradient (0% to 100% over 20 min)) to afford 1,1,1,3,3,3-hexafluoro-2-(4-(4-(1,3-thiazol-2-ylsulfonyl)-1-piperazinyl)phenyl)-2-propanol trifluoroacetate (36 mg) as a white powder. 1H NMR (300 MHz, CD3OD) δ 8.09 (d, J=3.1 Hz, 1H), 8.01 (d, J=3.1 Hz, 1H), 7.58 (d, J=8.5 Hz, 2H), 7.03 (d, J=8.9 Hz, 2H), 3.44 (m, 4H), 3.35 (m, 4H). m/z (ESI, +ve ion) 476.0 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=0.664 μM; GK-GKRP EC50 (LC MS/MS)=0.842 μM.

Workup

  1. concentrationthe reaction was concentrated
  2. dissolutionre-dissolved in methanol (3 mL)
  3. customThe crude material was purified by reverse-phase preparative HPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm)
  4. washeluting with a 0.1% TFA in CH3CN/H2O, gradient (0% to 100% over 20 min))

Sources & evidence

ORD record
ord-654bc5ec37784374bfe75c4b68b74c0e
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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