Dimethylformamide → HCID 11591156, compound

HRID 853895Notes

Reaction equation

HRID 853895 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[H-].[Na+].CC1C=CC(S(O[CH2:23][C@@H:24]2[CH2:28][CH2:27][CH2:26][N:25]2[S:29]([C:32]2[CH:40]=[CH:39][C:38]3[N:37]4[CH2:41][C:42]([CH3:46])([CH3:45])[CH2:43][N:44]=[C:36]4[C:35]4(OCCC[O:47]4)[C:34]=3[CH:33]=2)(=[O:31])=[O:30])(=O)=O)=CC=1.CN(C=O)C>C1COCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:23][C@@H:24]2[CH2:28][CH2:27][CH2:26][N:25]2[S:29]([C:32]2[CH:40]=[CH:39][C:38]3[N:37]4[CH2:41][C:42]([CH3:46])([CH3:45])[CH2:43][N:44]=[C:36]4[C:35](=[O:47])[C:34]=3[CH:33]=2)(=[O:31])=[O:30])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 90154-MethoxyphenolHCID 24758Sodium hydrideHCID 58932564HCID 58932564, compound

Product 1

HCID 11591156HCID 11591156, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-methoxy-phenol (0.420 mmol) in THF (3 mL) was added NaH (60% dispersion in mineral oil) (0.015 g, 0.063 mmol) and the reaction was stirred at rt for 1 hr. {(2S)-1-[(3′,3′-Dimethyl-3′,4′-dihydro-2′H-spiro[1,3-dioxane-2,10′-pyrimido[1,2-a]indol]-8′-yl)sulfonyl]pyrrolidin-2-yl}methyl 4-methylbenzenesulfonate (0.12 g, 0.21 mmol) in THF (2 mL)/DMF (2 mL) was then added and the reaction heated overnight at 100° C. The reaction was quenched with water and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (30/70). The resulting product was dissolved in CH2Cl2 (3 mL) and methanesulfonic acid (2 mL) was added and the solution was stirred at 50° C. overnight. The reaction mixture was poured onto ice, basified to pH 11 with ammonium hydroxide and extracted with EtOAc (3×). The combined organic extracts were dried over Na2SO4, filtered, concentrated and purified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (30/70) to give the title compound as a light yellow foam (0.031 g, 38%). NMR (400 Mz, DMSO-d6): consistent. MS: (ESI+) m/z 484.1 [M+H].

Workup

  1. temperaturethe reaction heated overnight at 100° C
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (3×)
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (30/70)
  8. dissolutionThe resulting product was dissolved in CH2Cl2 (3 mL)
  9. additionmethanesulfonic acid (2 mL) was added
  10. stirringthe solution was stirred at 50° C. overnight
  11. additionThe reaction mixture was poured onto ice
  12. extractionextracted with EtOAc (3×)
  13. dry with materialThe combined organic extracts were dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. custompurified on Biotage Si 12+M cartridge silica gel eluting with acetone/hexane (30/70)

Sources & evidence

ORD record
ord-e3f1e24774184b5c8511524e86fa9782
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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