Dichloromethane → HCID 9819543, compound

HRID 2305105Notes

Reaction equation

HRID 2305105 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1.C(N(CC)CC)C.[CH3:23][C:24]([CH3:28])([CH3:27])[C:25]#[CH:26].C(Cl)[Cl:30]>[OH-].[Na+].[Cu]I>[ClH:30].[ClH:30].[CH3:23][C:24]([CH3:28])([CH3:27])[C:25]#[C:26][C:2]1[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]2[CH2:14][CH2:13][CH2:12][N:11]2[CH3:15])[CH:5]=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 135123,3-Dimethyl-1-butyneHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 9819543HCID 9819543, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine (270 mg, 1 mmol) in 5 mL of CH2Cl2 was added triethylamine (0.5 mL), Pd(II) (19 mg), CuI (a catalytic amount) and 0.3 mL of 3,3-dimethyl-1-butyne (2 mmol). The reaction mixture was heated at reflux for 40 hours. The mixture was diluted with CH2Cl2, and 2 mL of 10% NaOH were added. The organic layer was separated and dried, and the solvent was removed under reduced pressure. The free base was purified by chromatography, eluting with 1 to 2% MeOH in CH2Cl2. MS (CI/NH3) m/z 273 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 1.32 (s, 9H), 1.80 (br m, 3H), 2.05 (m, 1H), 2.36 (m, 1H), 2.52 (s, 3H), 2.73 (m, 1H), 3.17 (m, 1H), 3.95 (m, 1H), 4.05 (m, 1H), 7.18 (m, 1H), 8.20 (m, 2H). The salt was prepared by treatment with HCl in Et2O, as described above, to give 100 mg of the title compound. MS (CI/NH3) m/z 273 (M+H)+. 1H NMR (D2O, 300 MHz) δ 8.44 (d, J=2.2, 1H), 8.40 (s, 1H), 8.01 (m, 1H), 4.61 (dd, J=2.9, 11.1, 1H), 4.54 (dd, J=5.5, 11.0, 1H), 3.96 (m, 1H), 3.26 (m, 1H), 3.05 (s, 3H), 2.41 (m, 1H), 2.22 (m, 1H), 2.10 (m, 2H). Anal. Calcd for C17H24N2O.2.0 HCl.0.4 H2O: C, 57.92; H, 7.66; N, 7.95. Found: C, 58.10; H, 7.74; N, 7.57. [α]25D=−7.70° (c 1.46, MeOH).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 40 hours
  3. additionwere added
  4. customThe organic layer was separated
  5. customdried
  6. customthe solvent was removed under reduced pressure
  7. customThe free base was purified by chromatography
  8. washeluting with 1 to 2% MeOH in CH2Cl2
  9. customThe salt was prepared by treatment with HCl in Et2O

Sources & evidence

ORD record
ord-11410871549e411a888edeeebbe0e955
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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