Hydrochloric Acid → HCID 89812843, compound

HRID 1481091Notes

Reaction equation

HRID 1481091 reaction equation
COC([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=O.[CH3:25][O-:26].[Na+].[CH3:28][OH:29].Cl.[CH3:31][OH:32]>O>[CH3:25][O:26][C:31](=[O:32])[C:13]([CH3:8])([CH3:12])[CH2:14][CH2:5][NH:6][C:28]([C:5]1[N:6]=[C:7]([C:23]#[N:24])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]=2)=[O:29]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 23694274Sodium methanolate methanolHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 89812843HCID 89812843, compoundYield 19%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (90 mg, 0.28 mmol) and 4-amino-2,2-dimethyl-butyric acid methyl ester, trifluoroacetic acid salt (290 mg, 1.12 mmol) in MeOH (0.5 mL) was added 0.5 M NaOMe/MeOH solution until the pH of the mixture reaches 8 (1.24 mL, 0.61 mmol was added). The resultant mixture was refluxed overnight. Reaction mixture was diluted with water (50 mL), acidified by 1 N HCl to pH=4 and then extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Residue was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexnaes. Fractions containing the desired product were collected and concentrated. The resultant solid was triturated with MeOH (2 mL). Solid was collected and dried in vacuo to provide the title compound 23 mg (0.053 mmol) in 19% yield. LC-MS ESI−: 432.13 (M−1)−.

Workup

  1. addition8 (1.24 mL, 0.61 mmol was added)
  2. customReaction mixture
  3. extractionextracted with EtOAc
  4. washOrganic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customResidue was purified by silica gel chromatography
  9. washeluting with 5-50% EtOAc/hexnaes
  10. additionFractions containing the desired product
  11. customwere collected
  12. concentrationconcentrated
  13. customThe resultant solid was triturated with MeOH (2 mL)
  14. customSolid was collected
  15. customdried in vacuo

Sources & evidence

ORD record
ord-516034fcaf59473a8991451edd294aba
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

Loading…