Chloride → HCID 54352653, compound

HRID 842046Notes

Reaction equation

HRID 842046 reaction equation
[H-].[Na+].[CH3:3][C:4]1[NH:5][C:6]([CH3:26])=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[C:24]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=3[C:18]([OH:25])=[CH:17][CH:16]=2)[N:10]=1.[CH2:27]([N:29]([CH2:32][CH2:33][O:34][CH2:35][CH2:36]Cl)[CH2:30][CH3:31])[CH3:28].[Cl-].[OH-].[Na+]>CN(C)C=O>[CH3:3][C:4]1[NH:5][C:6]([CH3:26])=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[C:24]3[CH2:23][CH2:22][CH2:21][CH2:20][C:19]=3[C:18]([O:25][CH2:36][CH2:35][O:34][CH2:33][CH2:32][N:29]([CH2:30][CH3:31])[CH2:27][CH3:28])=[CH:17][CH:16]=2)[N:10]=1

Participants

7

Reactant 5

HCID 312ChlorideHCID 14798Sodium HydroxideHCID 24758Sodium hydride2×HCID 15105203HCID 15105203, compoundHCID 135968514HCID 135968514, compound

Product 1

HCID 54352653HCID 54352653, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

To a three-necked 125 mL round-bottomed flask equipped with nitrogen (N2) inlet and septum were added 15 mL dry dimethylformamide and 50 mg (1.3 mmol) sodium hydride (washed with hexane). The reaction was cooled to 0° C., and a solution of 200 mg (0.6 mmol) 2-(2,5-dimethylpyrrolyl)-6-[4-hydroxy-5,6,7,8-tetrahydro-naphthalen-1-yl]-pyridine in 5 mL dry dimethylformamide added dropwise. The reaction was stirred 30 min at room temperature, then a solution of 234 mg (1.3 mmol) diethylaminoethoxy-ethyl chloride (J. Med. Chem., 34, 3159 (1991)) in 5 mL dry dimethylformamide added dropwise and the reaction heated at 100° C. for 20 hour, followed by more sodium hydride and chloride and heating another 24 hour The reaction was cooled, poured into aqueous sodium hydroxide solution, and extracted into ethyl acetate. The organic layer was washed with water, aqueous sodium bicarbonate solution, and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using methanol/methylene chloride as eluant to afford 83 mg (30%) of an oil. 1H-NMR (δ, CDCl3): 1.03 (t, J=7, 6H), 1.67 (m, 2H), 1.76 (m, 2H), 2.155 (s, 6H), 2.59 (q, J=7, 4H), 2.7-2.9 (m, 6H), 3.67 (t, J=7, 2H), 3.84 (t, J=6, 2H), 4.14 (t, J=6, 2H), 5.87 (s, 2H), 6.73 (d, J=8, 1H), 7.11 (d, J=8, 1H), 7.185 (d, J=8, 1H), 7.35 (d, J=8, 1H), 7.82 (t, J=8, 1H); 13C-NMR (δ, CDCl3): 11.68, 13.33, 22.30, 22.87, 23.68, 28.66, 47.61, 52.34, 67.65, 69.67, 70.10, 106.52, 107.80, 119.48, 122.95, 126.59, 127.68, 128.62, 132.55, 136.58, 137.84, 151.21, 156.85, 160.34; MS (%): 462 (parent+1, 100).

Workup

  1. customTo a three-necked 125 mL round-bottomed flask equipped with nitrogen (N2) inlet
  2. temperaturethe reaction heated at 100° C. for 20 hour
  3. temperatureheating another 24 hour The reaction
  4. temperaturewas cooled
  5. extractionextracted into ethyl acetate
  6. washThe organic layer was washed with water, aqueous sodium bicarbonate solution, and brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated
  9. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-bf5f1c4c11b24330853a5e46169a807f
Source dataset
uspto-grants-2002_04
Patent number
US06372768B1

Reaction notes

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