Dimethylformamide → HCID 11562826, compound

HRID 853899Notes

Reaction equation

HRID 853899 reaction equation
[Br:1][C:2]1(O)[CH:7]=[CH:6][CH:5]=[CH:4][NH:3]1.[H-].[Na+].CC1C=CC(S([O:21][CH2:22][C@@H:23]2[CH2:27][CH2:26][CH2:25][N:24]2[S:28]([C:31]2[CH:39]=[CH:38][C:37]3[N:36]4[CH2:40][C:41]([CH3:45])([CH3:44])[CH2:42][N:43]=[C:35]4[C:34]4(OCCC[O:46]4)[C:33]=3[CH:32]=2)(=[O:30])=[O:29])(=O)=O)=CC=1.CN(C=O)C>C1COCC1>[Br:1][C:2]1[C:7]([O:21][CH2:22][C@@H:23]2[CH2:27][CH2:26][CH2:25][N:24]2[S:28]([C:31]2[CH:39]=[CH:38][C:37]3[N:36]4[CH2:40][C:41]([CH3:44])([CH3:45])[CH2:42][N:43]=[C:35]4[C:34](=[O:46])[C:33]=3[CH:32]=2)(=[O:29])=[O:30])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 22000233HCID 22000233, compoundHCID 58932564HCID 58932564, compound

Product 1

HCID 11562826HCID 11562826, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-bromo pyridinol (0.089 g, 0.510 mmol) in THF (3 mL) was added NaH (60% dispersion in mineral oil) (0.020 g, 0.085 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 (0.100 g, 0.170 mmol) in THF (2 mL)/DMF (2 mL) was added and the reaction was 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 stirred at 35° 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 yellow foam (0.058 g, 56%). NMR (400 Mz, DMSO-d6): consistent. MS: (ESI+) m/z 533.1 [M+H].

Workup

  1. temperaturethe reaction was 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 stirred at 35° 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-11e02f8195a34f5bbb7cab80dea8cdc5
Source dataset
uspto-grants-2007_08
Patent number
US07256198B2

Reaction notes

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