Carbon Dioxide → 2,6-Dihydro-2-methyl-4-(2-methylpropyl)-6-phenylmethyl-1h-pyrrolo[3,4-d]pyridazin-1-one-5-carboxylic acid

HRID 1835155Notes

Reaction equation

HRID 1835155 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][N:14]1[C:19](=[O:20])[C:18]2=[CH:21][N:22]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:23]=[C:17]2[C:16]([CH2:31][CH:32]([CH3:34])[CH3:33])=[N:15]1.[C:35](=[O:37])=[O:36]>O1CCCC1>[CH3:13][N:14]1[C:19](=[O:20])[C:18]2=[CH:21][N:22]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:23]([C:35]([OH:37])=[O:36])=[C:17]2[C:16]([CH2:31][CH:32]([CH3:34])[CH3:33])=[N:15]1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 7912DiisopropylamineHCID 235032512,6-Dihydro-2-methyl-4-(2-methylpropyl)-6-phenylmethyl-1h-pyrrolo[3,4-d]pyridazin-1-oneHCID 178418339Butyllithium

Product 1

HCID 235032362,6-Dihydro-2-methyl-4-(2-methylpropyl)-6-phenylmethyl-1h-pyrrolo[3,4-d]pyridazin-1-one-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Butyl lithium (2.5M in hexanes, 2.35 m) was added dropwise to a stirred solution of diisopropylamine (0.85 ml) in dry tetrahydrofuran (10 ml) at 0° C., under nitrogen. The reaction was stirred at 0° C. for 30 minutes, then cooled to −78° C. To this was added a solution of 2,6-dihydro-2-methyl-4-(2-methylpropyl)-6-(1-phenylmethyl)-1H-pyrrolo[3,4-d]pyridazin-1-one (1.5 g, prepared as in Example 14 step b) in dry tetrahydrofuran (10 ml), and stirring was continued for 30 minutes. This anion was then added to an excess of solid carbon dioxide. The reaction was allowed to warm to room temperature overnight, and was then quenched by the addition of water. The mixture was extracted into ethyl acetate, washed with brine, dried and evaporated to give a yellow oil, which was chromatographed, eluting with ethyl acetate:isohexane(3:7), to give the sub-title compound as a yellow solid (0.91 g).

Workup

  1. temperaturecooled to −78° C
  2. stirringstirring
  3. waitwas continued for 30 minutes
  4. temperatureto warm to room temperature overnight
  5. customwas then quenched by the addition of water
  6. extractionThe mixture was extracted into ethyl acetate
  7. washwashed with brine
  8. customdried
  9. customevaporated
  10. customto give a yellow oil, which
  11. customwas chromatographed
  12. washeluting with ethyl acetate:isohexane(3:7)

Sources & evidence

ORD record
ord-01b903f348eb4822805d48b55299dab0
Source dataset
uspto-grants-2004_08
Patent number
US06770646B2

Reaction notes

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