Diisopropylethylamine → HCID 57505582, compound

HRID 2391341Notes

Reaction equation

HRID 2391341 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[O:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([CH:12]=[C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[N:14]=2)[N:11]=1.[CH3:24][N:25]1[CH2:32][CH2:31][CH2:30][C@H:26]1[C:27](O)=[O:28].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.OC1C2N=NNC=2C=CC=1.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH:18]1([C:16]([NH:15][C:13]2[N:14]=[C:9]3[CH:8]=[CH:7][C:6]([O:5][C:4]4[CH:3]=[C:2]([NH:1][C:27](=[O:28])[C@@H:26]5[CH2:30][CH2:31][CH2:32][N:25]5[CH3:24])[CH:23]=[CH:22][CH:21]=4)=[N:11][N:10]3[CH:12]=2)=[O:17])[CH2:20][CH2:19]1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 643474N-Methyl-L-prolineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamideHCID 178418300HCID 178418300, compound

Product 1

HCID 57505582HCID 57505582, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropylcarboxamide (200 mg, 0.65 mmol) in N,N-dimethylformamide (4.0 mL) were added 1-methyl-L-proline (167 mg, 1.29 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (736 mg, 1.94 mmol), hydroxybenzotriazole (262 mg, 1.94 mmol) and N,N-diisopropylethylamine (338 μL, 1.94 mmol), and the mixture was stirred at room temperature for 3 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/ethanol=8/1), and the obtained residue was recrystallized from ethyl acetate to give the title compound (86 mg, 32%) as a white powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltrated
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/ethanol=8/1)
  7. customthe obtained residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-412433e942d949baa6717038e5c33b23
Source dataset
uspto-grants-2012_09
Patent number
US08273741B2

Reaction notes

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