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

HRID 1481180Notes

Reaction equation

HRID 1481180 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[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].[NH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33].C[O-].[Na+]>>[OH:15][C:14]1[C:13]2[C:8](=[CH:9][C:10]([O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C:7]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[N:6][C:5]=1[C:3]([NH:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])=[O:4]

Participants

4

Reactant 3

HCID 239Beta-AlanineHCID 10942334Sodium MethoxideHCID 898129524-Hydroxy-7-phenoxy-1-phenyl-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 717357813-[(4-Hydroxy-7-phenoxy-1-phenyl-isoquinoline-3-carbonyl)-amino]-propionic acidYield 91.4%

Procedure

A mixture of 4-hydroxy-7-phenoxy-1-phenyl-isoquinoline-3-carboxylic acid methyl ester (46 mg, 0.12 mmol), β-alanine (552 mg, 6.2 mmol) and NaOMe (9.3 mL, 4.65 mmol, 0.5 M in MeOH) was refluxed for 16 h. After cooling to r.t., the solvent was evaporated. The residue was partitioned between EtOAc (50 mL) and water (50 mL). 1 M HCl was added with stirring until pH was ˜2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography (0-35% EtOAc/hexanes+2% AcOH) to give 47 mg of the title compound as a light yellow solid. MS: (+) m/z 429.13 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customthe solvent 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 (0-35% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-38a2b27735f0464591986907d5c59dbc
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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