Beta-Alanine → 3-[(1-Cyano-4-hydroxy-7-phenyl-isoquinoline-3-carbonyl)-amino]-propionic acid

HRID 1481165Notes

Reaction equation

HRID 1481165 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:22]#[N:23])[C:8]2[C:13]([C:14]=1[OH:15])=[CH:12][CH:11]=[C:10]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH:9]=2)=[O:4].[NH2:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28].C[O-].[Na+]>COCCO>[C:22]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:24][CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[O:4])[N:6]=1)#[N:23]

Participants

5

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 898129441-Cyano-4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 717357823-[(1-Cyano-4-hydroxy-7-phenyl-isoquinoline-3-carbonyl)-amino]-propionic acidYield 55.3%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenyl-isoquinoline-3-carboxylic acid methyl ester (46 mg, 0.15 mmol), β-alanine (674 mg, 7.57 mmol) and NaOMe (327 mg, 6.05 mmol) in 2-methoxyethanol (12 mL) was refluxed for 1.5 h. After the mixture was cooled to r.t., solvent was evaporated. The residue was partitioned between EtOAc (50 mL) and water (50 mL). 1 M HCl was added with vigorous stirring until pH was ˜2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography (0-60% EtOAc/hexanes+2% AcOH) to give 30 mg of the title compound as a pale pink solid. MS: (−) m/z 360.07 (M−1).

Workup

  1. temperaturewas refluxed for 1.5 h
  2. customsolvent was evaporated
  3. customThe residue was partitioned between EtOAc (50 mL) and water (50 mL)
  4. addition1 M HCl was added
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (0-60% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-e85c8151dde24edeb131b8fffc882055
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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