Sodium Methoxide → 3-{[1-(5-Fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl]amino}-2,2-dimethyl-propionic acid

HRID 1481163Notes

Reaction equation

HRID 1481163 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].OC(C(F)(F)F)=O.[NH2:37][CH2:38][C:39]([CH3:44])([CH3:43])[C:40]([OH:42])=[O:41].C[O-].[Na+]>CCO>[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:37][CH2:38][C:39]([CH3:44])([CH3:43])[C:40]([OH:42])=[O:41])=[O:4])[N:6]=2)[CH:24]=[N:25][CH:26]=1

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 898128461-(5-Fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl esterHCID 131732215HCID 131732215, compound

Product 1

HCID 717356193-{[1-(5-Fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl]amino}-2,2-dimethyl-propionic acidYield 48.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 1-(5-fluoro-pyridin-3-yl)-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (51 mg, 0.13 mmol), 3-amino-2,2-dimethyl-propionic acid TFA salt (121 mg, 0.52 mmol) and NaOMe (56 mg, 1.05 mmol) in EtOH (3 mL) was heated at 150° C. in a microwave reactor for 6 h. The solvent was evaporated, and the residue was partitioned between water (20 mL) and EtOAc (20 mL). 1 M HCl was added with vigorous stirring until pH was ˜3. 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 30 mg of the title compound as a yellow solid. MS: (+) m/z 476.14 (M+1).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between water (20 mL) and EtOAc (20 mL)
  3. addition1 M HCl was added
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (0-35% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-553125275815406eb402bff18fedf1e4
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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