Water → HCID 10132382, compound

HRID 397326Notes

Reaction equation

HRID 397326 reaction equation
[H-].[Na+].C(OC(=O)[NH:9][C@@H:10]([CH3:25])[CH2:11][C:12]1[C:20]2[CH:19]=[C:18]([OH:21])[CH:17]=[CH:16][C:15]=2[N:14]2[CH2:22][CH2:23][CH2:24][C:13]=12)(C)(C)C.[CH3:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][CH2:34]Br.O>CN(C)C=O.C(OCC)(=O)C>[CH3:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33][CH2:34][O:21][C:18]1[CH:17]=[CH:16][C:15]2[N:14]3[CH2:22][CH2:23][CH2:24][C:13]3=[C:12]([CH2:11][C@@H:10]([NH2:9])[CH3:25])[C:20]=2[CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 156361331-Bromo-3-(2-methoxyethoxy)propaneHCID 69364305HCID 69364305, compound

Product 1

HCID 10132382HCID 10132382, compoundYield 46.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

25 mg sodium hydride 55-65% in oil was added to a solution of 165 mg (S)-[2-(6-hydroxy-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester in 1.5 mL N,N-dimethylformamide. The mixture was stirred at room temperature for 30 min, then 120 mg 3-(methoxyethoxy)propyl bromide was added added and the reaction mixture was stirred at room temperature for an additional 22 h. The reaction mixture was distributed between water and ethyl acetate. The phases were separated, the organic phase washed with water, 10% citric acid, 10% sodium bicarbonate and brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with hexane:ethyl acetate=4:1. The product fractions were evaporated and the residue taken up in 4.0 mL of a 2.16 M solution of hydrochloric acid in ethyl acetate. The mixture was stirred at room temperature for 1 h, the solid collected by filtration, neutralised with aqueous ammonium hydroxide and purified by chromatography on silica gel with dichloromethane:methanol:aqueous ammonium hydroxide=90:9:1. The product fractions were dried over magnesium sulfate and evaporated to yield 80 mg (S)-2-{6-[3-(2-methoxy-ethoxy)-propoxy]-2,3-dihydro-1H-3a-aza-cyclopenta[a]inden-8-yl}-1-methyl-ethylamine as light brown oil. MS: M+H=347.5; M+H−NH3=330.4.

Workup

  1. additionadded
  2. stirringthe reaction mixture was stirred at room temperature for an additional 22 h
  3. customThe phases were separated
  4. washthe organic phase washed with water, 10% citric acid, 10% sodium bicarbonate and brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customThe residue was purified by chromatography on silica gel with hexane
  8. customThe product fractions were evaporated
  9. stirringThe mixture was stirred at room temperature for 1 h
  10. filtrationthe solid collected by filtration
  11. custompurified by chromatography on silica gel with dichloromethane
  12. dry with materialThe product fractions were dried over magnesium sulfate
  13. customevaporated

Sources & evidence

ORD record
ord-277f31d5761e46e08f06133187b8f9d4
Source dataset
uspto-grants-2003_08
Patent number
US06610685B2

Reaction notes

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