Dichloromethane → HCID 69830986, compound

HRID 1780318Notes

Reaction equation

HRID 1780318 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 methylene chloride 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, during with 2 to 6% methanol in methylene chloride. MS (CI/NH3) m/z 293 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ2.07 (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 ether, 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) δ8.39 (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 C19H20N2O·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, during with 2 to 6% methanol in methylene chloride
  5. customThe salt was prepared by treatment with HCl in ether

Sources & evidence

ORD record
ord-c508aef663b34e13a1fe771b31973a49
Source dataset
uspto-grants-1997_05
Patent number
US05629325

Reaction notes

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