Gabapentin → HCID 71737521, compound

HRID 1480998Notes

Reaction equation

HRID 1480998 reaction equation
[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21](OC)=[O:22])[N:4]=1)#[N:2].[CH2:25]1[CH2:30][CH2:29][C:28]([CH2:35][NH2:36])([CH2:31][C:32]([OH:34])=[O:33])[CH2:27][CH2:26]1.C[O-].[Na+]>COCCO>[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:11]=2)[C:6]([OH:20])=[C:5]([C:21]([NH:36][CH2:35][C:28]2([CH2:31][C:32]([OH:34])=[O:33])[CH2:29][CH2:30][CH2:25][CH2:26][CH2:27]2)=[O:22])[N:4]=1)#[N:2]

Participants

5

Reactant 3

HCID 3446GabapentinHCID 10942334Sodium MethoxideHCID 89812860Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate

Product 1

HCID 71737521HCID 71737521, compound

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Procedure

Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate (30 mg, 0.09 mmol), gabapentin (96 mg, 0.56 mmol, TCI) and sodium methoxide (28 mg, 0.53 mmol) were suspended in 2-methoxyethanol (3 mL). The resulting mixture was heated to reflux for 3 hours and then cooled to room temperature. The solvent was removed in vacuo and the residue was dissolved in H2O (15 mL) and EtOAc (15 mL). To the stirred mixture was added 1 N hydrochloric acid until pH was 1. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-50% EtOAc/hexanes with 0.5% formic acid) to give the title compound in 11 mg. MS: (−) m/z 458.00 (M-1).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 3 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in H2O (15 mL)
  5. additionTo the stirred mixture was added 1 N hydrochloric acid until pH was 1
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted twice with EtOAc
  8. dry with materialThe combined organic layers were dried over MgSO4
  9. concentrationconcentrated
  10. custompurified by flash chromatography (0-50% EtOAc/hexanes with 0.5% formic acid)

Sources & evidence

ORD record
ord-d72e24c4ef2b477387502da53bd2f2b5
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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