4,6-Dichloropyrimidine → 6-(6-Chloropyrimidin-4-yloxy)isoquinoline-1-carboxylic acid

HRID 1094525Notes

Reaction equation

HRID 1094525 reaction equation
C[O-].[Na+].[OH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([C:15]([OH:17])=[O:16])=[N:10][CH:9]=[CH:8]2.[Cl:18][C:19]1[CH:24]=[C:23](Cl)[N:22]=[CH:21][N:20]=1>CO.CN(C=O)C>[Cl:18][C:19]1[N:20]=[CH:21][N:22]=[C:23]([O:4][C:5]2[CH:6]=[C:7]3[C:12](=[CH:13][CH:14]=2)[C:11]([C:15]([OH:17])=[O:16])=[N:10][CH:9]=[CH:8]3)[CH:24]=1

Participants

6

Reactant 3

HCID 709434,6-DichloropyrimidineHCID 10942334Sodium MethoxideHCID 1363040466-Hydroxyisoquinoline-1-carboxylic acid

Product 1

HCID 866386236-(6-Chloropyrimidin-4-yloxy)isoquinoline-1-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

40 ml (20 mMol) of a 0.5 M solution of sodium methylate in MeOH are added to a suspension of 1.9 g (10 mMol) 6-hydroxy-isoquinoline-1-carboxylic acid (CAS 174299-07-1) in 50 ml MeOH and sonicated until a solution is obtained. The solvent is then evaporated off. The residue is dried in high vacuum for 4 h and 100 ml DMF are added. The suspension is cooled to 10° C. and a solution of 1.55 g (10 mMol) 4,6-dichloropyrimidine in 25 ml DMF is added. The reaction mixture is stirred at room temperature for 14 h. The solvent is evaporated off and the mixture is partitioned between H2O/EtOAc. After extraction, the aqueous phase is neutralized with a 1 N solution of HCl. The suspension is extracted with EtOAc, washed with H20 and brine, dried (MgSO4) and concentrated to give a beige powder: 1H-NMR (DMSO-d6): δ ppm 7.60 (s, 1H), 7.68 (dd, J=9.4, 2.3 Hz, 1H), 7.98 (d, J=2.3 Hz, 1H), 8.04 (d, J=5.5 Hz, 1H), 8.59 (d, J=5.9 Hz, 1H), 8.66 (s, 1H), 8.68 (s, 1H).

Workup

  1. customsonicated until a solution
  2. customis obtained
  3. customThe solvent is then evaporated off
  4. customThe residue is dried in high vacuum for 4 h
  5. addition100 ml DMF are added
  6. customThe solvent is evaporated off
  7. customthe mixture is partitioned between H2O/EtOAc
  8. extractionAfter extraction
  9. extractionThe suspension is extracted with EtOAc
  10. washwashed with H20 and brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customto give a beige powder

Sources & evidence

ORD record
ord-7f157121284f4e48bed72aeedcf010e6
Source dataset
uspto-grants-2012_03
Patent number
US08133886B2

Reaction notes

Loading…