Beta-Aminobutyric Acid → 3-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]butyric acid

HRID 1480944Notes

Reaction equation

HRID 1480944 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][CH:26]([CH3:31])[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][CH:26]([CH3:31])[CH2:27][C:28]([OH:30])=[O:29])=[O:4])[N:6]=1)#[N:24]

Participants

4

Reactant 3

HCID 10932Beta-Aminobutyric AcidHCID 23694274Sodium methanolate methanolHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 781645723-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]butyric acidYield 3.8%

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (110 mg, 0.34 mmol) and 3-amino-butyric acid (354 mg, 3.4 mmol) (Sigma-Aldrich Corp., St. Louis Mo.) in 0.5 M NaOMe/MeOH solution (5.4 mL<2.72 mmol) was refluxed overnight and then microwaved at 120° C. for 2 h. Reaction mixture was concentrated and residue was dissolved in water (60 mL). It was acidified by 1 N HCl to pH=3-4. Precipitate was collected, rinsed with water and dried. The crude product was purified by silica gel chromatography, eluting with 5-100% EtOAc (with 0.075% acetic acid)/hexane (with 0.1% acetic acid). White solid was crystallized from fractions containing the desired produce. Solid was collected and rinsed with EtOAc and dried in vacuo to provide the title compound 5.1 mg (0.013 mmol) in 3.8% yield. LC-MS ESI−: 390.01 (M−1)−.

Workup

  1. temperaturewas refluxed overnight
  2. custommicrowaved at 120° C. for 2 h
  3. customReaction mixture
  4. concentrationwas concentrated
  5. dissolutionresidue was dissolved in water (60 mL)
  6. customPrecipitate was collected
  7. washrinsed with water
  8. customdried
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 5-100% EtOAc (with 0.075% acetic acid)/hexane (with 0.1% acetic acid)
  11. customWhite solid was crystallized from fractions
  12. additioncontaining the
  13. customdesired produce
  14. customSolid was collected
  15. washrinsed with EtOAc
  16. customdried in vacuo

Sources & evidence

ORD record
ord-92dfd44e424d429d99efa25fbbc1ca8c
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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