Sodium hydride → HCID 69609138, compound

HRID 1836693Notes

Reaction equation

HRID 1836693 reaction equation
[H-].[Na+].[S:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][CH2:15][N:16]1[CH2:32][CH2:31][C:19]2([N:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][NH:21][C:20]2=[O:30])[CH2:18][CH2:17]1.Cl.[CH3:34][N:35]([CH2:37][CH2:38][Cl:39])[CH3:36]>CN(C=O)C>[ClH:39].[CH3:34][N:35]([CH3:36])[CH2:37][CH2:38][N:21]1[C:20](=[O:30])[C:19]2([CH2:18][CH2:17][N:16]([CH2:15][CH2:14][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=3[C:4]3[S:3][CH:7]=[CH:6][CH:5]=3)[CH2:32][CH2:31]2)[N:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:22]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 12150154HCID 12150154, compound

Product 1

HCID 69609138HCID 69609138, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a heterogenous mixture of unwashed 60% NaH dispersed in mineral oil (96.5 mg, 2.41 mmol) in DMF (3 mL) was added 8-[2-[2-(2-thienyl)phenyl]ethyl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one (prepared as in Example 5) (208.8 mg, 0.500 mmol). The mixture was stirred until H2 gas evolution was observed to stop (30 min), then treated with N,N-dimethylaminoethyl chloride hydrochloride (158 mg, 1.10 mmol). The resulting reaction mixture was stirred for an additional 18 h under argon atmosphere. The reaction was quenched with aqueous NH4Cl (50 mL), and the crude product was extracted into CHCl3 (2×40 mL). The organic extracts were washed with H2O (5×50 mL), dried over Na2SO4, filtered and concentrated to a crude oil. The crude oil was washed with hexane (3×50 mL) to remove mineral oil, then purified by Tapered prep TLC (6% MeOH in CHCl3) to yield title compound as a free base. The free base was dissolved in CHCl3 (15 mL) and treated with 1.0 mL of 1N HCl in Et2O. HCL salt was precipitated by addition of Et2O, collected by filtration and dried in the vacuum oven at 60° C. for 18 h to yield the title compound as a white amorphous solid.

Workup

  1. custom(30 min)
  2. customThe resulting reaction mixture
  3. stirringwas stirred for an additional 18 h under argon atmosphere
  4. customThe reaction was quenched with aqueous NH4Cl (50 mL)
  5. extractionthe crude product was extracted into CHCl3 (2×40 mL)
  6. washThe organic extracts were washed with H2O (5×50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a crude oil
  10. washThe crude oil was washed with hexane (3×50 mL)
  11. customto remove mineral oil
  12. custompurified by Tapered prep TLC (6% MeOH in CHCl3)

Sources & evidence

ORD record
ord-81ccbec0db064206b61ac11efae13e9c
Source dataset
uspto-grants-2004_08
Patent number
US06777421B2

Reaction notes

Loading…