3-(Aminomethyl)-5-methylhexanoic acid → 3-{[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-methyl}-5-methyl-hexanoic acid

HRID 1481238Notes

Reaction equation

HRID 1481238 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][CH:27]([CH2:32][CH:33]([CH3:35])[CH3:34])[CH2:28][C:29]([OH:31])=[O:30]>C[O-].[Na+].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:25][CH2:26][CH:27]([CH2:32][CH:33]([CH3:35])[CH3:34])[CH2:28][C:29]([OH:31])=[O:30])=[O:4])[N:6]=1)#[N:24]

Participants

5

Reactant 2

HCID 47151693-(Aminomethyl)-5-methylhexanoic acidHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 898128883-{[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-methyl}-5-methyl-hexanoic acidYield 48.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 10942334Sodium MethoxideSolvent

Procedure

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (50 mg, 0.16 mmole) and 3-(aminomethyl)-5-methylhexanoic acid (249 mg, 1.6 mmole, AK Scientific) in 0.5 M sodium methoxide in methanol (2.5 ml) was refluxed for two days before it was cooled to room temperature, concentrated and dissolved in water, extracted with dichloromethane. The remaining aqueous layer was acidified with 1N hydrochloric chloride, extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, concentrated and purified by flash column chromatography on silica gel with a gradient of dichloromethane and ethyl acetate to give the title compound as a white solid (35 mg). LC-MS ESI+: 448 (M+1)+; ESI−: 446 (M-1)−.

Workup

  1. temperaturewas refluxed for two days before it
  2. concentrationconcentrated
  3. dissolutiondissolved in water
  4. extractionextracted with dichloromethane
  5. extractionextracted with dichloromethane
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. custompurified by flash column chromatography on silica gel with a gradient of dichloromethane and ethyl acetate

Sources & evidence

ORD record
ord-22612ae01ef14d99a7f75aa4295769d4
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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