(S)-4-Amino-3-hydroxybutanoic acid → (S)-4-(1-Cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-3-hydroxybutanoic acid

HRID 1480997Notes

Reaction equation

HRID 1480997 reaction equation
[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21](OC)=[O:22])[N:4]=1)#[N:2].[NH2:25][CH2:26][C@@H:27]([OH:32])[CH2:28][C:29]([OH:31])=[O:30].C[O-].[Na+]>COCCO>[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21]([NH:25][CH2:26][C@@H:27]([OH:32])[CH2:28][C:29]([OH:31])=[O:30])=[O:22])[N:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 6971281(S)-4-Amino-3-hydroxybutanoic acidHCID 10942334Sodium MethoxideHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 71737524(S)-4-(1-Cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-3-hydroxybutanoic acid

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate (30 mg, 0.09 mmol), (S)-4-amino-3-hydroxybutanoic acid (67 mg, 0.56 mmol, Sigma-Aldrich) and sodium methoxide (28 mg, 0.53 mmol) were suspended in 2-methoxyethanol (3 mL). The resulting mixture was heated to reflux for 3 hours and then cooled to room temperature. The solvent was removed in vacuo and the residue was dissolved in H2O (15 mL) and EtOAc (15 mL). To the stirred mixture was added 1 N hydrochloric acid until pH was 1. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-50% EtOAc/hexanes with 0.5% formic acid) to give the title compound in 27 mg. MS: (−) m/z 406.00 (M−1).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 3 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in H2O (15 mL)
  5. additionTo the stirred mixture was added 1 N hydrochloric acid until pH was 1
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted twice with EtOAc
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated
  10. custompurified by flash chromatography (0-50% EtOAc/hexanes with 0.5% formic acid)

Sources & evidence

ORD record
ord-230ba2756f314f5a831bddd06b81ccf1
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

Loading…