Hydrochloric Acid → HCID 71736743, compound

HRID 1481100Notes

Reaction equation

HRID 1481100 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].[CH3:25][O-:26].[Na+].Cl.[OH2:29]>CCO>[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:6][CH2:5][C@H:14]([CH3:13])[C:25]([OH:29])=[O:26])=[O:4])[N:6]=1)#[N:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 10942334Sodium MethoxideHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 71736743HCID 71736743, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (50 mg, 0.16 mmol) and 3-amino-2-(S)-methyl-propionic acid, trifluoroacetic acid salt (48 mg, 0.47 mmol) in EtOH (2 mL) was added NaOMe solid (60 mg) (amount needed to adjust the pH of the mixture to 8-9). The resultant mixture was microwaved at 140° C. for 1 h. Reaction mixture was diluted with water (60 mL) and acidified by 1 N HCl to pH=3-4. It was extracted with EtOAc. Organic layer was dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography, eluting with 5-100% EtOAc/CH2Cl2, to provide the title compound 16.8 mg (0.043 mmol) in 28% yield. 1H NMR (200 MHz) in DMSO-d6, δ ppm: 14.78 (s, 1H), 12.37 (s, 1H), 9.29 (br s, 1H), 8.41 (d, J=9.2 Hz, 1H), 7.73 (br d, J=10.6 Hz, 1H), 7.54 (m, 2H), 7.30 (m, 4H), 3.58 (m, 1H), 3.43 (m, 1H), 2.81 (m, 1H), 1.10 (d, J=7.0 Hz, 3H).

Workup

  1. customReaction mixture
  2. extractionIt was extracted with EtOAc
  3. dry with materialOrganic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customCrude product was purified by silica gel chromatography
  7. washeluting with 5-100% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-39565f82db9e4638b8ca8ca0fa0a8336
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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