Acetone → CBL-0137 free base

HRID 1615023Notes

Reaction equation

HRID 1615023 reaction equation
[CH3:1][C:2]([CH3:4])=O.[NH2:5][CH2:6][CH2:7][N:8]1[C:20]2[CH:19]=[CH:18][C:17]([C:21](=[O:23])[CH3:22])=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[C:12]([C:24](=[O:26])[CH3:25])[CH:13]=2.C([O-])(O)=O.[Na+].Cl>C(Cl)Cl.O1CCOCC1.C(Cl)(Cl)Cl.CO>[CH:2]([NH:5][CH2:6][CH2:7][N:8]1[C:20]2[CH:19]=[CH:18][C:17]([C:21](=[O:23])[CH3:22])=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[C:12]([C:24](=[O:26])[CH3:25])[CH:13]=2)([CH3:4])[CH3:1]

Participants

8

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 45381115HCID 45381115, compound

Product 1

HCID 44519124CBL-0137 free base

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolventHCID 21584188Chloroform methanolSolvent

Procedure

Acetone (5 mL, 68.10 mmol) was added to a solution of compound 53 (1.25 g, 4.25 mmol) in CH2Cl2 (50 mL). Then STAB (3.0 g, 14.15 mmol) was added. The mixture obtained was stirred at room temperature for 4.5 h (TLC monitoring, eluent: CHCl3-MeOH, 9:1) and then poured into an aqueous solution of NaHCO3. The organic layer was separated. The aqueous layer was extracted with CH2Cl2. The product was dried over Na2SO4 and evaporated. The residue was purified on a column, eluent: CHCl3-MeOH 99:1→90:10. Example 7 (1.04 g, 73%) was isolated as a rapidly crystallizing oil. For the preparation of its hydrochloride, the base was dissolved in CH2Cl2. Then, a solution of HCl in dioxane was added. The mixture was evaporated to dryness. The product was washed with ether.

Workup

  1. additionThen STAB (3.0 g, 14.15 mmol) was added
  2. customThe mixture obtained
  3. customThe organic layer was separated
  4. extractionThe aqueous layer was extracted with CH2Cl2
  5. dry with materialThe product was dried over Na2SO4
  6. customevaporated
  7. customThe residue was purified on a column, eluent
  8. customa rapidly crystallizing oil
  9. customFor the preparation of its hydrochloride
  10. customThe mixture was evaporated to dryness
  11. washThe product was washed with ether

Sources & evidence

ORD record
ord-005cf90bf94642b9b0f0bde8e10f1c1d
Source dataset
uspto-grants-2014_07
Patent number
US08765738B2

Reaction notes

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