Methyl iodide → HCID 66748915, compound

HRID 1405933Notes

Reaction equation

HRID 1405933 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[C:19]3=[N:20][S:21](=[O:25])(=[O:24])[CH2:22][CH2:23][N:18]3[CH2:17][CH2:16][NH:15]2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C>[CH3:26][N:15]1[CH2:16][CH2:17][N:18]2[C:19](=[N:20][S:21](=[O:25])(=[O:24])[CH2:22][CH2:23]2)[C@@H:14]1[C:11]1[CH:12]=[CH:13][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 66747958HCID 66747958, compound

Product 1

HCID 66748915HCID 66748915, compoundYield 13.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (9S)-9-(4-phenoxyphenyl)-3,4,6,7,8,9-hexahydropyrazino[2,1-c][1,2,4]thiadiazine 2,2-dioxide (129 mg), potassium carbonate (100 mg) and iodomethane (0.022 mL) in DMF (4 mL) was stirred at 0° C. to room temperature for 20 hr. The reaction mixture was added with NH silica gel, evaporated, and purified by column chromatography (NH silica gel, eluted with EtOAc in hexane then 20% MeOH in EtOAc) then preparative HPLC (C18, MeCN in H2O with 0.1% TFA). The combined collected fractions were concentrated in vacuo. The resulting aqueous solution was added with NaHCO3 and NaCl, then extracted with EtOAc (2×100 mL). The organic layer was combined, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was recrystallized from EtOAc—IPE to give the title compound (18 mg) as a white solid.

Workup

  1. additionThe reaction mixture was added with NH silica gel
  2. customevaporated
  3. custompurified by column chromatography (NH silica gel
  4. washeluted with EtOAc in hexane
  5. customThe combined collected fractions
  6. concentrationwere concentrated in vacuo
  7. additionThe resulting aqueous solution was added with NaHCO3 and NaCl
  8. extractionextracted with EtOAc (2×100 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was recrystallized from EtOAc—IPE

Sources & evidence

ORD record
ord-396391f9273f4d09933e68c96d3c6476
Source dataset
uspto-grants-2014_12
Patent number
US08916551B2

Reaction notes

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