Potassium Carbonate → 7-bromo-3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}isoquinoline

HRID 860872Notes

Reaction equation

HRID 860872 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][C:14]2[N:15]=[CH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][CH:20]=[C:19]([Br:24])[CH:18]=3)(=O)=O)=CC=1.[CH3:25][C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:24][C:19]1[CH:18]=[C:17]2[C:22]([CH:23]=[C:14]([CH2:13][CH2:12][N:27]3[CH2:28][CH2:29][CH2:30][C@H:26]3[CH3:25])[N:15]=[CH:16]2)=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 641544(R)-2-MethylpyrrolidineHCID 865922262-(7-Bromo-3-isoquinolinyl)ethyl 4-methylbenzenesulfonate

Product 1

HCID 671046927-bromo-3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}isoquinoline

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The product from Example 52F was dissolved in a solution of (2R)-2-methylpyrrolidine (0.26 g, 3.0 mmol) in acetonitrile (20 mL). The solution was treated with potassium carbonate (0.5 g, 3.6 mmol) and heated at 50–55° C. for 20 hours in a sealed flask. The mixture was allowed to cool to room temperature, filtered, and the filtrate was concentrated in vacuo. The residue was diluted with MTBE (20 mL) and water (20 mL) and the pH was adjusted to 3–3.5 with concentrated HCl. The aqueous layer was separated, extracted with MTBE (10 mL), adjusted to a pH of 8–8.5 with potassium carbonate, and extracted with isopropyl acetate (20 mL). The organic layer was separated and concentrated in vacuo. The residue was dissolved in heptane (20 mL), filtered, and the filtrate concentrated under vacuum to provide the title compound. 1H NMR (CDCl3) δ 1.10 (d, J=6.1 Hz, 3H); 1.35–1.49 (m, 1H); 1.62–1.85 (m, 2H); 1.85–1.98 (m, 1H); 2.23 (q, J=8.8. Hz, 1H); 2.28–2.42 (m, 1H); 2.46–2.57 (m, 1H), 3.04–3.19 (m, 2H); 3.19–3.30 (m, 2H); 7.47 (s, 1H); 7.60 (d, J=8.8 Hz, 1H), 7.647.70 (m, 1H), 8.05 (m, 1H); 9.09 (s, 1H); HRMS Calcd. for [C16H19BrN2+H+]: 319.0810. Found: 319.0795.

Workup

  1. temperatureheated at 50–55° C. for 20 hours in a sealed flask
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionThe residue was diluted with MTBE (20 mL) and water (20 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with MTBE (10 mL)
  7. extractionextracted with isopropyl acetate (20 mL)
  8. customThe organic layer was separated
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in heptane (20 mL)
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated under vacuum

Sources & evidence

ORD record
ord-036fef13db7e4d428cab5074a245355e
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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