HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Triethylamine → 2-(4-{4-[(6-Aminopyridin-3-Yl)sulfonyl]piperazin-1-Yl}phenyl)-1,1,1,3,3,3-Hexafluoropropan-2-Ol

HRID 1972465
Notes
Print preview

Reaction equation

HRID 1972465 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].C([N:27](CC)CC)C.Cl[C:33]1[N:38]=[CH:37][C:36]([S:39](Cl)(=[O:41])=[O:40])=[CH:35][CH:34]=1.[OH-].[NH4+]>O.CCOC(C)=O.CCO.C(Cl)Cl>[NH2:27][C:33]1[N:38]=[CH:37][C:36]([S:39]([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:41])=[O:40])=[CH:35][CH:34]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 27927922-Chloro-5-pyridinesulfonyl chlorideHCID 866703461,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride

Product 1

HCID 736591502-(4-{4-[(6-Aminopyridin-3-Yl)sulfonyl]piperazin-1-Yl}phenyl)-1,1,1,3,3,3-Hexafluoropropan-2-Ol

Reagents, catalysts & solvents

4
HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 250-mL round-bottomed flask was charged with 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol dihydrochloride (2.50 g, 6.23 mmol), 20 mL of CH2Cl2, triethylamine (3.47 mL, 24.93 mmol), and 6-chloropyridine-3-sulfonyl chloride (1.32 g, 6.23 mmol, Organic Process Research & Development 2009, 13, 875). After stirring at room temperature for 30 min, water was added and the layers were separated. The organics were dried (MgSO4), filtered, and concentrated to give an oily solid. To this material was added 10 mL of EtOH and concentrated ammonium hydroxide (9.95 mL, 255 mmol). The vessel was sealed and heated at 120° C. for 12 h. After the mixture was allows to cool to room temperature, EtOAc (100 mL) and water (50 mL) were added. The organics were separated, dried (MgSO4), filtered and concentrated to give an oil. Purification via column chromatography on silica gel (0 to 70% EtOAc in hexanes) delivered 2-(4-(4-((6-amino-3-pyridinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1.65 g) as an off-white solid. 1H NMR (400 MHz, CD3OD) δ=8.30 (d, J=2.3 Hz, 1H), 7.74 (dd, J=2.4, 8.9 Hz, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.00 (d, J=9.0 Hz, 2H), 6.64 (d, J=8.8 Hz, 1H), 3.35-3.30 (m, 4H), 3.17-3.11 (m, 4H). m/z (ESI, +ve ion) 484.9 (M+H)+. GK-GKRP IC50 (Binding)=0.085 μM; GK-GKRP EC50 (LC MS/MS-2)=0.142 μM.

Workup

  1. customthe layers were separated
  2. dry with materialThe organics were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give an oily solid
  6. customThe vessel was sealed
  7. temperatureheated at 120° C. for 12 h
  8. temperatureto cool to room temperature
  9. customThe organics were separated
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give an oil
  14. customPurification via column chromatography on silica gel (0 to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-548e8fb16b294425998d8bd2abfc8dea
Source dataset
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08431563B2

Reaction notes

Loading…

On this pageParticipantsProcedureWorkupSources & evidenceReaction notes