Potassium Carbonate → tert-Butyl 4-(2-ethynyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718583Notes

Reaction equation

HRID 718583 reaction equation
[CH:1]([C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[N:7][N:6]2[C:17]=1[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:20][CH:19]=1)=O.[C:31]([O-])([O-])=O.[K+].[K+].[N+](=C(P(=O)(OC)OC)C(=O)C)=[N-]>CO.C(Cl)Cl>[C:1]([C:3]1[N:4]=[C:5]2[C:10]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:9][CH:8]=[N:7][N:6]2[C:17]=1[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])=[CH:20][CH:19]=1)#[CH:31]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 117732456tert-Butyl 4-(2-formyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoateHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-one

Product 1

HCID 117732463tert-Butyl 4-(2-ethynyl-8-morpholinoimidazo[1,2-b]pyridazin-3-yl)benzoate

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a suspension of compound 5f (0.30 g, 0.73 mmol, Example 5) in MeOH (5 mL) was added K2CO3 (0.30 g, 2.2 mmol) and a solution of dimethyl (1-diazo-2-oxopropyl)phosphonate (0.18 g, 0.96 mmol) in MeOH (2 mL). The reaction mixture was stirred at rt for 2 days, and concentrated under reduced pressure. The residue obtained was dissolved in DCM (20 mL) and washed with water (20 mL). The aqueous layer was extracted with DCM (3×10 mL). The combined organic extracts were washed with brine, and dried over MgSO4. The mixture was filtered and concentrated to give a residue, which was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane) to give the compound 17a as an off-white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C23H24N4O3: 405.2 (M+H). found: 405.2.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue obtained
  3. washwashed with water (20 mL)
  4. extractionThe aqueous layer was extracted with DCM (3×10 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationThe mixture was filtered
  8. concentrationconcentrated
  9. customto give a residue, which
  10. customwas purified by flash column chromatography on silica gel (20-60% EtOAc/heptane)

Sources & evidence

ORD record
ord-85c80da6de3e427fb50b884ca8346a35
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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