Triethylamine → 2-(4-(4-((6-Chloropyridazin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972533Notes

Reaction equation

HRID 1972533 reaction equation
Cl.Cl.[F:3][C:4]([F:24])([F:23])[C:5]([C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1)([OH:10])[C:6]([F:9])([F:8])[F:7].[Cl:25][C:26]1[N:31]=[N:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1.C(N(CC)CC)C>C(=O)(O)[O-].[Na+].C(Cl)Cl>[Cl:25][C:26]1[N:31]=[N:30][C:29]([S:32]([N:20]2[CH2:21][CH2:22][N:17]([C:14]3[CH:13]=[CH:12][C:11]([C:5]([OH:10])([C:6]([F:9])([F:8])[F:7])[C:4]([F:3])([F:23])[F:24])=[CH:16][CH:15]=3)[CH2:18][CH2:19]2)(=[O:34])=[O:33])=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 616113006-Chloropyridazine-3-sulfonyl chloride2×HCID 866703461,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride

Product 1

HCID 569326312-(4-(4-((6-Chloropyridazin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 34.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a 20 mL vial was added 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (0.35 g, 0.87 mmol, Example 91), 6-chloropyridazine-3-sulfonyl chloride (0.20 g, 0.96 mmol, Archiv der Pharmazie and Berichte der Deutschen Pharmazeutischen Gesellschaft 1966, 229, 646), CH2Cl2 (10 mL) and triethylamine (0.61 mL, 4.4 mmol). After 24 h at room temperature, an additional 100 mg of 6-chloropyridazine-3-sulfonyl chloride was added and the solution was stirred for an additional hour. The reaction was diluted with saturated aqueous sodium bicarbonate and CH2Cl2. This was stirred for 5 min and then 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 collected solution was purified by silica gel chromatography (0 to 70% EtOAc in hexanes). The resulting oil was dissolved in EtOAc/heptanes, concentrated and dried under reduced pressure to afford 2-(4-(4-((6-chloropyridazin-3-yl)sulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.15 g) as a yellow solid.

Workup

  1. stirringThis was stirred for 5 min
  2. customthe solution was transferred onto a phase separation cartridge (Radleys Discovery Technologies, Essex, UK) with the organic phase
  3. custombeing collected
  4. customThe collected solution was purified by silica gel chromatography (0 to 70% EtOAc in hexanes)
  5. dissolutionThe resulting oil was dissolved in EtOAc/heptanes
  6. concentrationconcentrated
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-8ff31001c37a4e658c10f9faba54eacb
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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