1-Hydroxybenzotriazole → HCID 57505622, compound

HRID 1668074Notes

Reaction equation

HRID 1668074 reaction equation
[CH3:1][N:2]1[CH2:9][CH2:8][CH2:7][C@H:3]1[C:4]([OH:6])=O.[NH2:10][C:11]1[CH:12]=[C:13]([CH:30]=[CH:31][C:32]=1[CH3:33])[O:14][C:15]1[CH:16]=[CH:17][C:18]2[N:19]([CH:21]=[C:22]([NH:24][C:25]([CH:27]3[CH2:29][CH2:28]3)=[O:26])[N:23]=2)[N:20]=1.ON1C2C=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:27]1([C:25]([NH:24][C:22]2[N:23]=[C:18]3[CH:17]=[CH:16][C:15]([O:14][C:13]4[CH:30]=[CH:31][C:32]([CH3:33])=[C:11]([NH:10][C:4](=[O:6])[C@@H:3]5[CH2:7][CH2:8][CH2:9][N:2]5[CH3:1])[CH:12]=4)=[N:20][N:19]3[CH:21]=2)=[O:26])[CH2:28][CH2:29]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 643474N-Methyl-L-prolineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57505476N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505622HCID 57505622, compoundYield 5.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-methyl-L-proline (170 mg, 1.3 mmol), N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (210 mg, 0.65 mmol), 1-hydroxybenzotriazole (175 mg, 1.3 mmol), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (490 mg, 1.3 mmol), N,N-diisopropylethylamine (330 mg, 2.6 mmol) and N,N-dimethylformamide (15 mL) was stirred at room temperature for 18 hr, and then at 40° C. for 4 hr. The solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and water were added to the residue, the aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90) to give the title compound (15 mg, 5%) as a white solid.

Workup

  1. waitat 40° C. for 4 hr
  2. customThe solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and water
  3. additionwere added to the residue
  4. extractionthe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×4)
  5. washCombined organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltrated
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→10/90)

Sources & evidence

ORD record
ord-3daa920dcd3b4ab89df266ef1081ff0c
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

Loading…