Dichloromethane → HCID 69830986, compound

HRID 2305104Notes

Reaction equation

HRID 2305104 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.[C:23]1([C:29]#[CH:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(Cl)[Cl:32]>[Cu]I>[ClH:32].[ClH:32].[C:23]1([C:29]#[C:30][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:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 112887213-Bromo-5-((S)-1-methyl-pyrrolidin-2-ylmethoxy)-pyridine

Product 1

HCID 69830986HCID 69830986, compound

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

To a solution of 5-bromo-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine (272 mg, 1 mmol) in 6 mL of CH2Cl2 was added triethylamine (0.5 mL), Pd(II) (19 mg), CuI (a catalytic amount) and 0.22 mL of phenylacetylene (2 mmol). The reaction mixture was heated at reflux for 40 hours. The solvent was removed under reduced pressure, and the free base was purified by chromatography, eluting with 2 to 6% MeOH in CH2Cl2. MS (CI/NH3) m/z 293 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ 2.07 (m, 2H), 2.25 (m, 2H), 2.81 (m, 1H), 2.88 (s, 3H), 3.47 (m, 1H), 3.67 (m, 1H), 4.23 (m, 1H), 4.64 (m, 1H), 7.38 (m, 4H), 7.54 (m, 2H), 8.28 (m, 1H), 8.42 (m, 1H). The salt was prepared by treatment with HCl in Et2O, as described above to give 90 mg of the title compound. mp 190-192° C. MS (CI/NH3) m/z 293 (M+H)+. 1H NMR (D2O, 300 MHz) δ 8.39 (d, J=1.5, 1H), 8.30 (d, J=2.6, 1H), 7.65 (m, 3H), 7.48 (m, 3H), 4.54 (dd, J=3.3, 11.0, 1H), 4.38 (dd, J=5.9, 11.4, 1H), 3.94 (br, 1H), 3.26 (br, 1H), 3.05 (s, 3H), 2.41 (m, 1H), 21.4 (m, 1H), 2.09 (m, 2H). Anal. Calcd for C19H20N2.2.2 HCl: C, 61.25; H, 6.01; N, 7.52. Found: C, 61.14; H, 5.84; N, 7.52. [α]25D=−10.00° (c 0.22, MeOH).

Workup

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

Sources & evidence

ORD record
ord-af95db2ca99a4871a89548345d2db08c
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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