Ethanol → HCID 56932425, compound

HRID 1972469Notes

Reaction equation

HRID 1972469 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([OH:32])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:33].CCO.[OH-].[NH4+:38]>O>[NH2:38][C:2]1[N:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([OH:32])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][C:3]=1[F:33]

Participants

5

Reactant 3

HCID 702EthanolHCID 14923Ammonium HydroxideHCID 86670349HCID 86670349, compound

Product 1

HCID 56932425HCID 56932425, compoundYield 53.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
125 °C

Procedure

A 100-mL pressure vessel was charged with 2-(4-(4-((6-chloro-5-fluoro-3-pyridinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.725 g, 1.389 mmol), 5 mL of EtOH, and concentrated ammonium hydroxide (10 mL, 257 mmol). The vessel was sealed and the mixture was heated to 125° C. for 18 h. After that time, the mixture was diluted with water and extracted with CH2Cl2 (3×100 mL). The combined extracts were dried (MgSO4), filtered and concentrated. The residue was purified by column chromatography on silica gel (0 to 70% EtOAc in hexanes) and to give 2-(4-(4-((6-amino-5-fluoro-3-pyridinyl)sulfonyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.375 g) as a white solid. 1H NMR (400 MHz, CD3OD) δ=8.18 (d, J=1.4 Hz, 1H), 7.62 (dd, J=1.9, 10.5 Hz, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.01 (d, J=9.0 Hz, 2H), 3.35-3.29 (m, 4H), 3.19-3.14 (m, 4H). m/z (ESI, +ve ion) 503.1 (M+H)+. GK-GKRP IC50 (Binding)=0.163 μM; GK-GKRP EC50 (LC MS/MS-2)=0.299 μM.

Workup

  1. customThe vessel was sealed
  2. extractionextracted with CH2Cl2 (3×100 mL)
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (0 to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-6439fd82a1e7494bb3b7fba8b704eedd
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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