Hydrochloric Acid → HCID 71656209, compound

HRID 1428682Notes

Reaction equation

HRID 1428682 reaction equation
[OH:1][CH2:2][C:3]1[C:11]2[C:6](=[N:7][C:8]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)[N:10]=2)[N:5]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([O:34]CC)=[O:33])[CH:4]=1.[H-].[Na+].[CH3:39]I.Cl>CN(C=O)C.O>[CH3:39][O:1][CH2:2][C:3]1[C:11]2[C:6](=[N:7][C:8]([C:19]3[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=3)=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)[N:10]=2)[N:5]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[CH:4]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 71657496HCID 71657496, compound

Product 1

HCID 71656209HCID 71656209, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyl 7-(7-(hydroxymethyl)-2,3-di-p-tolyl-5H-pyrrolo[2,3-b]pyrazin-5-yl)heptanoate (Example 3) (50 mg, 0.103 mmol) in dry DMF (1 ml) under nitrogen was treated with NaH (60% in mineral oil) (4.53 mg, 0.113 mmol) and the resulting mixture was stirred at RT for 15 minutes. Methyl iodide (7.08 μl, 0.113 mmol) was added and stirring continued at RT overnight. The mixture was added to water (30 ml) and the pH was adjusted to pH1 by addition of 2M HCl. The aqueous was extracted with DCM (×3) and the combined organic portions were passed through a phase separating column and concentrated under reduced pressure. The crude product was purified by chromatography on silica eluting with 0-50% EtOAc/iso-hexane. Further purification was carried out by dissolving the product in DCM (minimal) and loading onto a 20 cm×20 cm preparative TLC plate. The plate was run using a solvent system of 67% EtOAc in iso-hexane (300 ml) and the appropriate strip of silica was scrapped off the plate. The Si was suspended in 10% MeOH/DCM and sonicated. The suspension was filtered, rinsing the solid with 10% MeOH/DCM. The filtrate was concentrated under reduced pressure to afford the title compound;

Workup

  1. stirringstirring
  2. waitcontinued at RT overnight
  3. extractionThe aqueous was extracted with DCM (×3)
  4. customseparating column
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by chromatography on silica eluting with 0-50% EtOAc/iso-hexane
  7. customFurther purification
  8. dissolutionby dissolving the product in DCM (minimal)
  9. customsonicated
  10. filtrationThe suspension was filtered
  11. washrinsing the solid with 10% MeOH/DCM
  12. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-1cd2bc5b16074cb6a7e6953c9d7e1eab
Source dataset
uspto-grants-2015_01
Patent number
US08937069B2

Reaction notes

Loading…