Hydrochloric Acid → HCID 89813166, compound

HRID 1480938Notes

Reaction equation

HRID 1480938 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][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:4].[CH3:23][O-:24].[Na+].[CH3:26][OH:27].Cl>O>[CH3:23][O:24][C:26](=[O:27])[C:13]([CH3:8])([CH3:12])[CH2:14][CH2:5][NH:6][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH:9]=2)=[O:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 23694274Sodium methanolate methanolHCID 86709142Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 89813166HCID 89813166, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (80 mg, 0.27 mmol) and 4-amino-2,2-dimethyl-butyric acid methyl ester, trifluoroacetic acid salt (210 mg, 0.81 mmol) in 0.5 M NaOMe/MeOH solution (1.62 mL, 0.81 mmol) was microwaved at 130° C. for 3 h. The reaction mixture was diluted with water (50 mL), acidified by 1 N HCl to pH=3-4 and then extracted with EtOAc. Organic layer was washed with water, brine, dried over MgSO4, filtered and concentrated. Residue was purified by silica gel chromatography, eluting with 5-50% EtOAc/hexanes, to provide the title compound 26 mg (0.063 mmol) in 23.6% yield. 1H NMR in CDCl3, δ ppm: 13.23 (s, 1H), 8.40 (s, 1H), 8.32 (d, J=8.8 Hz, 1H), 7.97 (br t, 1H), 7.42 (m, 4H), 7.12 (m, 3H), 3.64 (s, 3H), 3.52 (m, 2H), 1.95 (dd, J=9.1, 5.9 Hz, 2H), 1.27 (s, 6H).

Workup

  1. customwas microwaved at 130° C. for 3 h
  2. extractionextracted with EtOAc
  3. washOrganic layer was washed with water, brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customResidue was purified by silica gel chromatography
  8. washeluting with 5-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-db22ce45e1d54a3d9d3290f350480d8d
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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