5-Aminovaleric acid → 5-{[1-(5-Fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl]-amino}-pentanoic acid

HRID 1481184Notes

Reaction equation

HRID 1481184 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:23]2[CH:24]=[N:25][CH:26]=[C:27]([F:29])[CH:28]=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].[NH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36].C[O-].[Na+]>>[F:29][C:27]1[CH:28]=[C:23]([C:7]2[C:8]3[C:13](=[CH:12][CH:11]=[C:10]([O:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH:9]=3)[C:14]([OH:15])=[C:5]([C:3]([NH:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[O:4])[N:6]=2)[CH:24]=[N:25][CH:26]=1

Participants

4

Reactant 3

HCID 1385-Aminovaleric acidHCID 10942334Sodium MethoxideHCID 898128461-(5-Fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester

Product 1

HCID 898130795-{[1-(5-Fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl]-amino}-pentanoic acidYield 53.4%

Procedure

A mixture of 1-(5-fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (50 mg, 0.13 mmol), 5-aminovaleric acid (751 mg, 6.41 mmol) and NaOMe (10 mL, 5.13 mmol, 0.5 M in MeOH) was refluxed for 16 h. After cooling the mixture to r.t., the solvent was evaporated. The residue was partitioned between water and EtOAc. 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 (5-50% EtOAc/hexanes+2% AcOH) to give 33 mg of the title compound as an off-white solid. MS: (+) m/z 476.12 (M+1).

Workup

  1. temperaturewas refluxed for 16 h
  2. customthe solvent was evaporated
  3. customThe residue was partitioned between water and EtOAc
  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 (5-50% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-292fd164d4074c778736ca6124699062
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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