Trifluoroacetic acid → 5-hydroxy-2-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]pyridin-4(1H)-one

HRID 1056903Notes

Reaction equation

HRID 1056903 reaction equation
[OH:1][CH:2]([C:4]1[N:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH:30]=[N:29][CH:28]=3)[CH:22]=2)[CH:6]=[C:7]([O:11]CC2C=CC(OC)=CC=2)[C:8](=[O:10])[CH:9]=1)[CH3:3].FC(F)(F)C(O)=O>ClCCl>[OH:11][C:7]1[C:8](=[O:10])[CH:9]=[C:4]([CH:2]([OH:1])[CH3:3])[N:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[CH:30]=[N:29][CH:28]=3)[CH:22]=2)[CH:6]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 674192012-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]-5~[(4-methoxybenzyl)oxy]pyridin-4(1H)-one

Product 1

HCID 674057165-hydroxy-2-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]pyridin-4(1H)-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 25 mL round bottom flask containing 2-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]-5˜[(4-methoxybenzyl)oxy]pyridin-4(1H)-one was added 5 mL 1:1 (v/v) dichloromethane:trifluoroacetic acid and the solution was stirred at room temperature for 30 minutes and turned deep red. Concentration under nitrogen stream, purification by reversed phase HPLC (2 cm×5 cm CI 8, acetonitrile-water gradient, 0.05% TFA added), and elution from an SCX column (50 g, sulfonic acid, rinsed with MeOH, eluted with 1 N N¾ in MeOH) afforded 5-hydroxy-2-(1-hydroxyethyl)-1-[3-(isoquinolin-4-yl)phenyl]pyridin-4(1H)-one. ′H NMR (599 MHz, DMSO, 75° C.): 6 9.35 (s, 1H); 8.51 (s, 1H); 8.22 (d, J−8.2 Hz, 1H); 7.90 (d, J=8.5 Hz, 1H); 7.81 (t, J=7.7 Hz, 1H); 7.77-7.69 (m, 3H); 7.61 (s, 1H); 7.58 (d, J−7.8 Hz, 1H); 7.39 (s, 1H); 6.48 (s, 1H); 4.44 (q, J=6.4 Hz, 1H); 1.24 (d, J−6.4 Hz, 3H). HRMS (FT/ICR) calc 359.1390 (M+H)+ 359.1395 found.

Workup

  1. concentrationConcentration under nitrogen
  2. customstream, purification
  3. additionby reversed phase HPLC (2 cm×5 cm CI 8, acetonitrile-water gradient, 0.05% TFA added), and elution from an SCX column (50 g, sulfonic acid
  4. washrinsed with MeOH
  5. washeluted with 1 N N¾ in MeOH)

Sources & evidence

ORD record
ord-34cf1c9163ed42ed832dcd3f1400a1a0
Source dataset
uspto-grants-2016_07
Patent number
US09399651B2

Reaction notes

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