Iodine → (6S)-8-Ethyl-10-methoxy-N,6-dimethyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-4-carboxamide

HRID 494118Notes

Reaction equation

HRID 494118 reaction equation
[CH2:1]([N:3]1[CH2:20][C@H:19]([CH3:21])[N:18]2[C:5](=[C:6]([O:22][CH3:23])[C:7]3[C:12](=[O:13])[NH:11][N:10]=[C:9]([C:14]([NH:16]N)=[O:15])[C:8]=32)[C:4]1=[O:24])[CH3:2].[CH3:25]N.II.S([O-])([O-])=O.[Na+].[Na+]>ClCCl>[CH2:1]([N:3]1[CH2:20][C@H:19]([CH3:21])[N:18]2[C:5](=[C:6]([O:22][CH3:23])[C:7]3[C:12](=[O:13])[NH:11][N:10]=[C:9]([C:14]([NH:16][CH3:25])=[O:15])[C:8]=32)[C:4]1=[O:24])[CH3:2]

Participants

6

Reactant 4

HCID 807IodineHCID 6329MethylamineHCID 24437Sodium SulfiteHCID 68863914(6S)-8-ethyl-10-methoxy-6-methyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-4-carbohydrazide

Product 1

HCID 68864941(6S)-8-Ethyl-10-methoxy-N,6-dimethyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (6S)-8-ethyl-10-methoxy-6-methyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-4-carbohydrazide (0.39 g, 1.2 mmol) and methylamine (5.9 mL, 11.8 mmol; 2 M in THF) in anhydrous dichloromethane (25 mL) in a water bath at room temperature, a solution of iodine (0.60 g, 2.4 mmol) in dichloromethane was added dropwise. After the addition was completed, an aqueous solution of sodium sulfite was added and the mixture was stirred vigorously for 10 minutes. The organic phase was separated, diluted with chloroform, and washed with brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was triturated with a mixture of ethanol (7 mL) and diethyl ether (25 mL). The white solid precipitated was obtained by filtration and dried from its solution in toluene under vacuum.

Workup

  1. additionAfter the addition
  2. customThe organic phase was separated
  3. additiondiluted with chloroform
  4. washwashed with brine
  5. extractionThe organic extract
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was triturated with a mixture of ethanol (7 mL) and diethyl ether (25 mL)
  10. customThe white solid precipitated
  11. customwas obtained by filtration
  12. dry with materialdried from its solution in toluene under vacuum

Sources & evidence

ORD record
ord-bcb6ba50b57c4fe9ab9859bb3534a2b7
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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