Hydrochloric Acid → HCID 71735616, compound

HRID 1481211Notes

Reaction equation

HRID 1481211 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]([C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=1)[CH2:27][C:28]([OH:30])=[O:29].C[O-].[Na+].Cl>CN(C)C(=O)C.O>[Cl:37][C:33]1[CH:32]=[C:31]([CH:26]([NH:25][C:3]([C:5]2[N:6]=[C:7]([C:23]#[N:24])[C:8]3[C:13]([C:14]=2[OH:15])=[CH:12][CH:11]=[C:10]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:9]=3)=[O:4])[CH2:27][C:28]([OH:30])=[O:29])[CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 27641783-amino-3-(3-chlorophenyl)propanoic acidHCID 10942334Sodium MethoxideHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 71735616HCID 71735616, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

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-3-(3-chloro-phenyl)-propionic acid (156 mg, 0.78 mmol) (commercially available from Alfa Aesar L19797) in N,N-dimethylacetamide (DMA) (2 mL) was added sodium methoxide (34 mg, 0.62 mmol). The resultant suspension mixture was heated in a 150° C. oil bath for 4 h. After cooled, reaction mixture was diluted with water (50 mL), acidified by 1 N HCl to pH=3-4, and then extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by silica gel chromatography, eluting with EtOAc/hexanes (10%-100%), to provide the title compound 20 mg (0.04 mmol) in 26% yield. LC-MS ESI−: 486 (M−1)−.

Workup

  1. temperatureAfter cooled
  2. customreaction mixture
  3. extractionextracted with EtOAc
  4. washOrganic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customCrude product was purified by silica gel chromatography
  9. washeluting with EtOAc/hexanes (10%-100%)

Sources & evidence

ORD record
ord-e875f4cd012544d09ff0e2ca2f639c62
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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