Acetic Acid → HCID 58382237, compound

HRID 1627997Notes

Reaction equation

HRID 1627997 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH2:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]3[CH:26]=[N:25][N:24]([CH3:27])[C:22]3=2)[N:17]([S:28]([C:31]2[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=2)(=[O:30])=[O:29])[CH:16]=1)[CH3:14].[I:38]I.CC(O)=O.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O.O>[CH2:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]3[CH:26]=[N:25][N:24]([CH3:27])[C:22]3=2)[N:17]([S:28]([C:31]2[CH:32]=[CH:33][C:34]([CH3:35])=[CH:36][CH:37]=2)(=[O:30])=[O:29])[C:16]=1[I:38])[CH3:14]

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 807IodineHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 58382318HCID 58382318, compoundHCID 178418339Butyllithium

Product 1

HCID 58382237HCID 58382237, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

Diisopropylamine (0.260 mL, 1.83 mmol) in THF (5 mL) was cooled to about −70° C. then the n-BuLi (1.6 M in hexanes, 1.04 mL, 1.67 mmol) was added drop-wise. The mixture was stirred at about −70° C. for about 15 min then allowed to warm to about 20° C. The resulting solution was added drop-wise to the 8-ethyl-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.295 g, 0.832 mmol) in THF (5 mL) at about −60 to −70° C. then the mixture was stirred for about 1 h. Iodine (0.239 g, 0.942 mmol) in THF (2 mL) was added drop-wise to the mixture and then it was stirred at about −70° C. for about 1 h. The reaction was treated with AcOH (0.143 mL, 2.50 mmol) then about 1 mL of saturated aqueous NH4Cl was added then the solution was warmed to rt. The mixture was diluted with EtOAc (50 mL) and water (20 mL) then the layers were separated. The organic layer was washed with saturated aqueous NaCl (20 mL) then dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was purified on a 10 g silica gel column with 94:6 DCM/EtOAc as an eluent to give 8-Ethyl-7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.155 g, 39%): LC/MS (Table 2, Method a) Rt=2.78 min; MS m/z 481 (M+H)+.

Workup

  1. temperatureto warm to about 20° C
  2. stirringthe mixture was stirred for about 1 h
  3. stirringit was stirred at about −70° C. for about 1 h
  4. temperaturethe solution was warmed to rt
  5. customthe layers were separated
  6. washThe organic layer was washed with saturated aqueous NaCl (20 mL)
  7. dry with materialthen dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe material was purified on a 10 g silica gel column with 94:6 DCM/EtOAc as an eluent

Sources & evidence

ORD record
ord-e854362962e4443eb2e58b90d4e9def4
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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