Triethylamine → HCID 86670394, compound

HRID 1972540Notes

Reaction equation

HRID 1972540 reaction equation
[Br:1][C:2]1[C:3]([S:7](Cl)(=[O:9])=[O:8])=[CH:4][S:5][CH:6]=1.Cl.Cl.[F:13][C:14]([F:34])([F:33])[C:15]([C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:23][CH:22]=1)([OH:20])[C:16]([F:19])([F:18])[F:17].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Br:1][C:2]1[C:3]([S:7]([N:30]2[CH2:31][CH2:32][N:27]([C:24]3[CH:23]=[CH:22][C:21]([C:15]([OH:20])([C:14]([F:13])([F:34])[F:33])[C:16]([F:19])([F:17])[F:18])=[CH:26][CH:25]=3)[CH2:28][CH2:29]2)(=[O:9])=[O:8])=[CH:4][S:5][CH:6]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27946384-bromothiophene-3-sulfonyl ChlorideHCID 866703461,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride

Product 1

HCID 86670394HCID 86670394, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 20 mL vial containing 4-bromothiophene-3-sulfonyl chloride (0.20 g, 0.77 mmol, ASDI, Newark, Del.) was added a solution of 1,1,1,3,3,3-hexafluoro-2-(4-(piperazin-1-yl)phenyl)-2-propanol dihydrochloride (0.31 g, 0.77 mmol, Example 91) and triethylamine (0.53 mL, 3.8 mmol) in CH2Cl2 (7 mL). The solution was stirred at room temperature for 16 h. To the vial was added saturated aqueous sodium bicarbonate (4 mL) and the solution was stirred for 15 min. The solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase being collected and passed through a plug of Na2SO4. The resulting solution was concentrated and purified by Prep-HPLC (Instrumentation: MS—Waters SQ; UV—Waters 2487 or Waters PD, Waters, Milford, Mass. Solvents: A: Water w/0.1% NH4OH B: Acetonitrile w/0.1% NH4OH. Column: Phenomenex Gemini-NX C18 110 Å 5 μm 21×100. Flow Rate: 44 mL/min. 10 min Method, variable gradient over 8 min. Mass spectral data were acquired from 100-850 amu in electrospray positive mode) to afford 2-(4-(4-(4-bromothiophen-3-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (81 mg) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.43 (br s, 1H), 8.08 (d, J=5.1 Hz, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.37 (d, J=5.1 Hz, 1H), 7.02 (d, J=9.0 Hz, 2H), 3.31-3.35 (m, 4H), 3.26-3.29 (m, 4H). m/z (ESI, +ve ion) 552.8 (M+H)+. GK-GKRP IC50 (Binding)=0.816 μM.

Workup

  1. stirringthe solution was stirred for 15 min
  2. customThe solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase
  3. custombeing collected
  4. concentrationThe resulting solution was concentrated
  5. custompurified by Prep-HPLC (Instrumentation
  6. wait10 min Method, variable gradient over 8 min

Sources & evidence

ORD record
ord-25c5e4a13b61494fb537238916e6d7ee
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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