Sodium hydride → HCID 18706968, compound

HRID 1422069Notes

Reaction equation

HRID 1422069 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3=[CH:24][C:25]([CH2:26][OH:27])=[C:21]4[N:22]3[C:17](=[CH:18][CH:19]=[CH:20]4)[C:16]=2[CH2:28][CH3:29])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CC(C)([O-])C.[K+].Cl.[CH3:39][N:40]([CH3:45])[CH2:41][CH2:42][CH2:43]Cl>CN(C)C=O.O.C(O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[C:23]3=[CH:24][C:25]([CH2:26][O:27][CH2:43][CH2:42][CH2:41][N:40]([CH3:45])[CH3:39])=[C:21]4[N:22]3[C:17](=[CH:18][CH:19]=[CH:20]4)[C:16]=2[CH2:28][CH3:29])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 943083-(Dimethylamino)propyl chloride hydrochlorideHCID 10883437HCID 10883437, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 18706968HCID 18706968, compoundYield 47.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(4-Benzyloxyphenyl)-1-ethyl-4-hydroxymethylpyrrolo[2,1,5-cd]indolizine (1.0 g, 2.62 mmol) was dissolved in 100 ml of dry dimethylformamide under nitrogen atmosphere. Sodium hydride (60% in oil) (1.23 g, 30.8 mmol) and potassium-t-butoxide (0.03 g, 0.26 mmol) was added in portions and stirring was continued for ten minutes. 3-Dimethylamino-1-propylchloride hydrochloride (1.24 g, 7.84 mmol) was added, and the solution was stirred for twenty-four hours. Ethanol (20 ml) was added dropwise, and the reaction mixture was diluted with 250 ml of water. The organic material was extracted into ethyl acetate (2×100 ml), and the combined organic layers were dried over sodium hydrogen carbonate. The solvent was evaporated and the crude product was purified by column chromatography over silica gel 60, using 10% of methanol in dichloromethane as the eluent to afford 0.58 g (47%) of 2-(4-benzyloxyphenyl)-4-((3-dimethylaminopropoxy)methyl)-1-ethylpyrrolo[2,1,5-cd]indolizine as yellow crystals. M.p. 63-65° C. MS(SP): m/z 466 (M+). 1H-NMR (CDCl3, 300 MHz) δ: 1.47 (t, 3H); 1.82 (m, 2H); 2.23 (s, 6H); 2.39 (t, 2H); 3.24 (q, 2H); 3.61 (t, 2H); 5.01 (s, 2H); 5.17 (s, 2H); 7.15 (d, 2H); 7.32-7.52 (m, 5H); 7.53 (s, 1H); 7.64 (t, 1H); 7.73 (d, 2H); 7.91 (d, 1H); 7.99 (d, 1H).

Workup

  1. waitwas continued for ten minutes
  2. stirringthe solution was stirred for twenty-four hours
  3. extractionThe organic material was extracted into ethyl acetate (2×100 ml)
  4. dry with materialthe combined organic layers were dried over sodium hydrogen carbonate
  5. customThe solvent was evaporated
  6. customthe crude product was purified by column chromatography over silica gel 60

Sources & evidence

ORD record
ord-6b440ef9502b4bea997b208698c9ee21
Source dataset
uspto-grants-2000_06
Patent number
US06080754

Reaction notes

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