1-Methylpyrrolidine → HCID 67110891, compound

HRID 409265Notes

Reaction equation

HRID 409265 reaction equation
[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10](Br)[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4].[C:27]([Cu])#[N:28].CN1CCCC1>O>[CH2:1]([O:5][C:6]([C:8]1[N:9]=[C:10]([C:27]#[N:28])[C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][C:14]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)=[CH:13][CH:12]=2)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 84541-MethylpyrrolidineHCID 86595482HCID 86595482, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 67110891HCID 67110891, compoundYield 76.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 1-bromo-6-cyclohexyloxy-4-hydroxy-isoquinoline-3-carboxylic acid butyl ester (see U.S. Patent Application Publication No. 2004/0254215; 350 mg, 0.83 mmol), CuCN (149 mg, 1.66 mmol) and N-methyl-pyrrolidine (2.5 mL) was heated at 130° C. for 2 h. After cooled, reaction mixture was poured into water (50 mL) with stirring. Precipitate was collected and rinsed with water. Resulting solid was partitioned between ethyl acetate and 10% aqueous NH4OH (50 mL), and vigorously stirred for 15 min. The mixture was acidified by aqueous concentrated HCl and then 1 N HCl solution to pH=4. The organic phase was separated and the aqueous phase was extracted with ethyl acetate. Combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated to give the title product (234 mg). MS-(+)-ion: M+1=369.43.

Workup

  1. temperatureAfter cooled
  2. customreaction mixture
  3. customPrecipitate was collected
  4. washrinsed with water
  5. customResulting solid
  6. customwas partitioned between ethyl acetate and 10% aqueous NH4OH (50 mL)
  7. stirringvigorously stirred for 15 min
  8. customThe organic phase was separated
  9. extractionthe aqueous phase was extracted with ethyl acetate
  10. washCombined organic layers were washed with brine
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-b10c67a91f8c4a47997cc7d6e6aaad8e
Source dataset
uspto-grants-2014_06
Patent number
US08759373B2

Reaction notes

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