Dichloromethane → HCID 69830116, compound

HRID 1780321Notes

Reaction equation

HRID 1780321 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.[CH:23]#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(Cl)[Cl:32]>[OH-].[Na+].[Cu]I>[ClH:32].[ClH:32].[C:23]([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:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]

Participants

7

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 123701-OctyneHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 69830116HCID 69830116, 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 (272 mg, 0.1 mmol) in 6 mL of methylene chloride was added triethylamine (0.4 mL), Pd(II) (18 mg), CuI (a catalytic amount) and 0.3 mL of 1-octyne (0.2 mmol). The reaction mixture was heated at reflux for 40 hours. The mixture was diluted with methylene chloride, 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 was purified by chromatography, eluting with 1 to 2% methanol in methylene chloride. MS (CI/NH3) m/z 301 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ0.91 (μ, 3H), 1.32 (μ, 4H), 1.60 (μ, 2H), 1.90 (μ, 3H), 2.15 (μ, 1H), 2.42 (μ, 2H), 2.64 (σ, 3H), 2.98 (βρ σ, 1H), 3.34 (βρ σ, 1H), 4.04 (μ, 1H), 4.25 (μ, 1H), 7.22 (μ, 1H), 8.22 (μ, 2H). The salt was prepared by treatment with HCl in ether, as described above, to give 110 mg of the title compound. MS (CI/NH3) m/z 301 (M+H)+. 1H NMR (D2O, 300 MHz) δ8.45 (d, J=2.6, 1H), 8.42 (d, J=1.1, 1H), 8.07 (m, 1H), 4.63 (dd, J=3.0, 11.1, 1H), 4.47 (dd, J=5.9, 11.4, 1H), 3.97 (m, 1H), 3.78 (m, 1H), 3.27 (m, 1H), 3.05 (s, 3H), 2.51 (t, J=7.0, 2H), 2.42 (m, 1H), 2.23 (m, 1H), 2.10 (m, 2H), 1.63 (m, 2H), 1.44 (m, 2H), 1.33 (m, 4H), 0.88 (m, 3H). Anal. Calcd for C19H28N2O·2.0 HCl: C, 61.12; H, 8.10; N, 7.50. Found: C, 60.99; H, 7.89; N, 7.28. [α]25D =-4.00° (c 1.75, 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 was purified by chromatography
  8. washeluting with 1 to 2% methanol in methylene chloride
  9. customThe salt was prepared by treatment with HCl in ether

Sources & evidence

ORD record
ord-9d69431ab11248ac9b90863c94a09e0d
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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