Dichloromethane → HCID 69831038, compound

HRID 1780320Notes

Reaction equation

HRID 1780320 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([CH2:21][CH3:22])CC)C.C[C:24]1[CH:29]=[CH:28][C:27]([C:30]#[CH:31])=[CH:26]N=1.C(Cl)[Cl:33]>[OH-].[Na+].[Cu]I>[ClH:33].[ClH:33].[CH3:26][C:27]1[CH:28]=[CH:29][C:24]([C:21]#[C:22][C:2]2[CH:3]=[C:4]([O:8][CH2:9][C@@H:10]3[CH2:14][CH2:13][CH2:12][N:11]3[CH3:15])[CH:5]=[N:6][CH:7]=2)=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 6381975-Ethynyl-2-methylpyridineHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 69831038HCID 69831038, 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 (200 mg, 0.7 mmol) in 5 mL of methylene chloride was added triethylamine (0.4 mL), Pd(II) (12 mg), CuI (a catalytic amount) and 0.15 mL of 2-methyl-5-ethynylpyridine (0.14 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 base was purified by chromatography, eluting with 1 to 2% methanol in methylene chloride. MS (CI/NH3) m/z 307 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.50 (m, 3H), 1.79 (m, 3H), 2.04 (m, 1H), 2.30 (m, 1H), 2.50 (s, 3H), 2.67 (m, 1H), 3.12 (m, 1H), 3.98 (m, 2H), 7.18 (m, 2H), 7.32 (m, 1H), 7.43 (m, 2H), 8.26 (m, 1H). The salt was prepared by treatment with HCl in ether, as described above, to give 120 mg of the title compound. mp 197°-199° C. MS (CI/NH3) m/z 307 (M+H)+. 1H NMR (D2O, 300 MHz) δ8.49 (d, J=1.5, 1H), 8.42 (d, J=2.6, 1H), 7.98 (m, 1H), 7.55 (d, J=8.1 (2H), 7.32 (d, J=7.7, 2H), 4.60 (dd, J=3.0, 11.1, 1H), 4.44 (dd, J=5.9, 11.4, 1H), 3.96 (m, 1H), 3.77 (m, 1H), 3.26 (m, 1H), 3.05 (s, 3H), 2.41 (m, 1H), 2.38 (s, 3H), 2.23 (m, 1H), 2.12 (m, 2H). Anal. Calcd for C22H24N2O·2.0 HCl·1.1 H2O: C, 60.18; H, 6.62; N, 7.02. Found: C, 59.98; H, 6.58; N, 6.77. [α]25D =-3.70° (c 0.54, 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% methanol in methylene chloride
  9. customThe salt was prepared by treatment with HCl in ether

Sources & evidence

ORD record
ord-62e1dc4aea7f4d8294ca4c7174560d93
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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