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

HRID 1480943Notes

Reaction equation

HRID 1480943 reaction equation
CO[C:3]([C:5]1[N:6]=[C:7]([C:23]#[N:24])[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].[NH2:25][CH2:26][CH2:27][C:28]([OH:30])=[O:29]>C[O-].[Na+].CO>[C:23]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:25][CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:4])[N:6]=1)#[N:24]

Participants

4

Reactant 2

HCID 239Beta-AlanineHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 898130203-[(1-Cyano-4-hydroxy-7 phenoxy-isoquinoline-3-carbonyl)-amino]-propionic acidYield 24%

Reagents, catalysts & solvents 1

HCID 23694274Sodium methanolate methanolSolvent

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (88 mg, 0.27 mmol) and beta-alanine (122 mg, 1.38 mmol) in 2.2 ml of 0.5 M NaOMe/MeOH solution was microwaved at 120° C. for 10 min. Reaction mixture was concentrated. The residue was dissolved in water (80 ml) and extracted with EtOAc, which was discarded. The aqueous layer was acidified by 1 N HCl to pH=3-4 and extracted with EtOAc. Organic layer was dried over MgSO4, filtered and concentrated. The crude product was triturated with hot MeOH and then CH2Cl2. Solid was collected and dried to provide the title compound 24 mg (0.064 mmol) in 24% yield.

Workup

  1. customwas microwaved at 120° C. for 10 min
  2. customReaction mixture
  3. concentrationwas concentrated
  4. dissolutionThe residue was dissolved in water (80 ml)
  5. extractionextracted with EtOAc, which
  6. extractionextracted with EtOAc
  7. dry with materialOrganic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was triturated with hot MeOH
  11. customSolid was collected
  12. customdried

Sources & evidence

ORD record
ord-d36550d5a5264970a68d042ed1c5a577
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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