Hydrochloric Acid → HCID 71737232, compound

HRID 1481068Notes

Reaction equation

HRID 1481068 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].Cl.[NH2:26][C@H:27]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:28][C:29]([OH:31])=[O:30].C[O-].[Na+].[OH-].[Na+].Cl>COCCO.CO>[C:23]([C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([O:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:9]=2)[C:14]([OH:15])=[C:5]([C:3]([NH:26][C@H:27]([CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:28][C:29]([OH:31])=[O:30])=[O:4])[N:6]=1)#[N:24]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 10942334Sodium MethoxideHCID 24820568(3R)-3-Amino-4-phenylbutanoic acid--hydrogen chloride (1/1)HCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 71737232HCID 71737232, compoundYield 56.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80192-MethoxyethanolSolvent

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (40 mg, 0.125 mmol), (R)-3-amino-4-phenyl-butyric acid HCl salt (270 mg, 1.25 mmol) (PepTech Corporation), and NaOMe (101 mg, 1.88 mmol) in 2-methoxyethanol (10 mL) was refluxed for 1.5 h. The resulting mixture was concentrated in vacuo, and the residue was partitioned between EtOAc and water. Hydrochloric acid (1 M) was added with vigorous stirring until pH ˜2. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH). The compound isolated was then dissolved in MeOH (2 mL) and treated with 2 M NaOH (2 mL) for 2 h. Hydrochloric acid (1 M) was added to acidify the mixture, and the mixture was extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated. The residue was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH) to give 33 mg of the title compound. MS: (+) m/z 468.06 (M+1).

Workup

  1. temperaturewas refluxed for 1.5 h
  2. concentrationThe resulting mixture was concentrated in vacuo
  3. customthe residue was partitioned between EtOAc and water
  4. additionHydrochloric acid (1 M) was added
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH)
  8. customThe compound isolated
  9. extractionthe mixture was extracted with EtOAc
  10. dry with materialThe organic layer was dried over MgSO4
  11. concentrationconcentrated
  12. customThe residue was purified by column chromatography (5-40% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-16ea4682a3a7418a91d743b98bfd7413
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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