4-Amino-3,3-dimethylbutanoic acid hydrochloride → 4-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-3,3-dimethyl-butyric acid

HRID 1481096Notes

Reaction equation

HRID 1481096 reaction equation
CO[C:3]([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:4].Cl.[NH2:26][CH2:27][C:28]([CH3:34])([CH3:33])[CH2:29][C:30]([OH:32])=[O:31]>C[O-].[Na+].CO>[C:23]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:26][CH2:27][C:28]([CH3:34])([CH3:33])[CH2:29][C:30]([OH:32])=[O:31])=[O:4])[N:6]=1)#[N:24]

Participants

4

Reactant 2

HCID 144354354-Amino-3,3-dimethylbutanoic acid hydrochlorideHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 898130014-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-3,3-dimethyl-butyric acidYield 7.8%

Reagents, catalysts & solvents 1

HCID 23694274Sodium methanolate methanolCatalyst

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (70 mg, 0.22 mmol) and 4-amino-3,3-dimethyl-butyric acid HCl salt (110 mg, 0.66 mmol) (Oakwood Products) in 0.5 M NaOMe/MeOH (2.62 mL, 1.3 μmol) was microwaved at 120° C. for 1 h. Reaction mixture was concentrated and residue was dissolved in water (50 mL), It was acidified by 1 N HCl to pH=3-4 and extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by chromatography, eluting with 50-100% EtOAc/hexanes to provide the title compound 7.2 mg (0.017 mmol) in 7.8% yield. LC-MS ESI−: 417.95 (M-1)−.

Workup

  1. customwas microwaved at 120° C. for 1 h
  2. customReaction mixture
  3. concentrationwas concentrated
  4. dissolutionresidue was dissolved in water (50 mL)
  5. extractionextracted with EtOAc
  6. washOrganic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customCrude product was purified by chromatography
  11. washeluting with 50-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-e0e63a380adf4c79935caea2bae6db6b
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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