Rolipram → 1-[(7-Chloro-2-quinolinyl)methyl]4-[3(cyclopentyloxy)-4methoxyphenyl]-2-pyrrolidinone

HRID 2395402Notes

Reaction equation

HRID 2395402 reaction equation
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[CH2:19][NH:18][C:17](=[O:20])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[CH2:24][C:25]1[CH:34]=[CH:33][C:32]2[C:27](=[CH:28][C:29]([Cl:35])=[CH:30][CH:31]=2)[N:26]=1>CN(C=O)C.O>[Cl:35][C:29]1[CH:28]=[C:27]2[C:32]([CH:33]=[CH:34][C:25]([CH2:24][N:18]3[CH2:19][CH:15]([C:9]4[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]5[CH2:2][CH2:3][CH2:4][CH2:5]5)[CH:8]=4)[CH2:16][C:17]3=[O:20])=[N:26]2)=[CH:31][CH:30]=1

Participants

6

Reactant 3

HCID 5092RolipramHCID 24758Sodium hydrideHCID 109548447-Chloro-2-(chloromethyl)quinoline

Product 1

HCID 189718301-[(7-Chloro-2-quinolinyl)methyl]4-[3(cyclopentyloxy)-4methoxyphenyl]-2-pyrrolidinone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-[3-Cyclopentyloxy-4-methoxyphenyl]-2-pyrrolidinone (1.00 g, 3.63 mmol, 1.0 eq) was added to a room temperature suspension of (145 mg, 3.63 mmol, 1.0 eq) NaH (60% oil dispersion) in 30 ml of anhydrous DMF. After stirring at room temperature for 1 hour, (0.77 g, 3.63 mmol, 1.0 eq) 2-chloromethyl-7-chloroquinoline was added, and the reaction mixture was allowed to stir at room temperature for 60 hours. The reaction mixture was then diluted with 250 mL H2O and extracted with ethyl acetate. The ethyl acetate extract was washed twice with H2O, once with brine, dried over Na2SO4 and concentrated to yield a yellow oil. Silica gel chromatography eluting with 5% CH3OH/CH2Cl2 followed by recrystallization from ethyl acetate-hexane yielded 0.61 g, 37%, of white crystals. M.P.: 106°-107° C. Elemental Analysis Calc'd for C26H27N2O3Cl: Calc'd: C, 69.15; H, 6.03; N, 6.21. Found: C, 69.22; H, 5.75; N, 615.

Workup

  1. stirringto stir at room temperature for 60 hours
  2. extractionextracted with ethyl acetate
  3. extractionThe ethyl acetate extract
  4. washwas washed twice with H2O, once with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto yield a yellow oil
  8. washSilica gel chromatography eluting with 5% CH3OH/CH2Cl2
  9. customfollowed by recrystallization from ethyl acetate-hexane
  10. customyielded 0.61 g, 37%

Sources & evidence

ORD record
ord-b83e28f85fe24fc29feb2e3d43a67b4e
Source dataset
uspto-grants-1998_09
Patent number
US05814651

Reaction notes

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