Z-Dap-OH → HCID 89813055, compound

HRID 1481094Notes

Reaction equation

HRID 1481094 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][C@H:27]([NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])[C:28]([OH:30])=[O:29].C[O-].[Na+]>COCCO>[CH2:35]([O:34][C:32]([NH:31][C@@H:27]([CH2:26][NH:25][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:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH:9]=2)=[O:4])[C:28]([OH:30])=[O:29])=[O:33])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

5

Reactant 3

HCID 2756313Z-Dap-OHHCID 10942334Sodium MethoxideHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 89813055HCID 89813055, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

To mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (200 mg, 0.63 mmol) and 3-amino-2-(S)-benzyloxycarbonylamino-propionic acid (745 mg, 3.12 mmol) (Bachem) in 2-methoxyethanol (10 mL) was added NaOMe solid (135 mg, 2.5 mmol). The resultant mixture was refluxed overnight. Reaction mixture was concentrated. Residue was dissolved in water (100 mL) and acidified by 1 N HCl to pH=3-4. Precipitate was collected, rinsed with water and dried. It was purified by silica gel chromatography, eluting with 10-100% EtOAc (with 0.075% acetic acid)/CH2Cl2 (with 0.01% acetic acid) to provide the title compound 91 mg (0.17 mmol) in 28% yield. LC-MS ESI−: 525.05 (M−1)−.

Workup

  1. customReaction mixture
  2. concentrationwas concentrated
  3. dissolutionResidue was dissolved in water (100 mL)
  4. customPrecipitate was collected
  5. washrinsed with water
  6. customdried
  7. customIt was purified by silica gel chromatography
  8. washeluting with 10-100% EtOAc (with 0.075% acetic acid)/CH2Cl2 (with 0.01% acetic acid)

Sources & evidence

ORD record
ord-deb1c9b7bc9a4865adcb81d69dda724a
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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