Sodium Hydroxide → 3{-[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-3-methyl-butyric acid

HRID 1481111Notes

Reaction equation

HRID 1481111 reaction equation
C(O[C:6]([C:8]1[N:9]=[C:10]([C:27]#[N:28])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])CCC.[NH2:29][C:30]([CH3:36])([CH3:35])[CH2:31][C:32]([OH:34])=[O:33].C[O-].[Na+].[OH-].[Na+]>CN(C=O)C.O>[C:27]([C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:19][C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)[CH:12]=2)[C:17]([OH:18])=[C:8]([C:6]([NH:29][C:30]([CH3:36])([CH3:35])[CH2:31][C:32]([OH:34])=[O:33])=[O:7])[N:9]=1)#[N:28]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 27609333-Amino-3-methylbutanoic acidHCID 10942334Sodium MethoxideHCID 671101121-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester

Product 1

HCID 898129643{-[1-Cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-3-methyl-butyric acidYield 35.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-cyano-7-(4-fluoro-phenoxy)-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (60 mg, 0.16 mmol) and 3-amino-3-methyl-butyric acid (92 mg, 0.79 mmol) in DMF (1.5 mL) was added NaOMe solid (34 mg, 0.63 mmol). The resultant mixture was stirred in a 150-160° C. oil bath for 4 h. Reaction mixture was diluted with water (60 mL) and basified by 1 N NaOH to pH=10. It was extracted with EtOAc (30 mL), which was discarded. Aqueous layer was acidified by 1 N HCl to pH=3-4. Precipitate was collected and dried. Crude product was then triturated with MeOH (4 mL). Solid was collected and dried in vacuo to provide the title compound 24 mg (0.057 mmol) in 35% yield. LC-MS ESI−: 422.07 (M−1)−.

Workup

  1. customReaction mixture
  2. extractionIt was extracted with EtOAc (30 mL), which
  3. customPrecipitate was collected
  4. customdried
  5. customCrude product was then triturated with MeOH (4 mL)
  6. customSolid was collected
  7. customdried in vacuo

Sources & evidence

ORD record
ord-17814f9e43534b53805892d253315713
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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