Ethanol, 2-(aminooxy)- → HCID 58190589, compound

HRID 1959729Notes

Reaction equation

HRID 1959729 reaction equation
[F:1][C:2]1[C:10]([CH:11]([C:13]2[N:17]3[N:18]=[C:19]([C:22](=O)[CH3:23])[CH:20]=[CH:21][C:16]3=[N:15][CH:14]=2)[CH3:12])=[C:9]([F:25])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH3:26].[NH2:27][O:28][CH2:29][CH2:30][OH:31]>CO>[OH:31][CH2:30][CH2:29][O:28]/[N:27]=[C:22](/[C:19]1[CH:20]=[CH:21][C:16]2[N:17]([C:13]([CH:11]([C:10]3[C:2]([F:1])=[C:3]4[C:7](=[CH:8][C:9]=3[F:25])[N:6]([CH3:26])[N:5]=[CH:4]4)[CH3:12])=[CH:14][N:15]=2)[N:18]=1)\[CH3:23]

Participants

4

Reactant 2

HCID 3014186Ethanol, 2-(aminooxy)-2×HCID 581905801-(3-(1-(4,6-Difluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazin-6-yl)ethanone

Product 1

HCID 58190589HCID 58190589, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 1-(3-(1-(4,6-difluoro-1-methyl-1H-indazol-5-yl)ethyl)imidazo[1,2-b]pyridazin-6-yl)ethanone (110 mg, 0.31 mmol) and 2-(aminooxy)ethanol (intermediate S) (35.1 mg, 0.31 mmol) in 10 mL of MeOH was stirred at it overnight. Solvent was evaporated and the residue was partitioned between water and EtOAc. Aqueous layer was extracted with EtOAc twice. Organic layers were combined, washed with brine and dried over Na2SO4. Solvent was evaporated and the crude was purified by HPLC (basic with 0.05% NH4OH) to give 55 mg (43%) of the title compound as white solid. 1H-NMR (400 MHz, MeOH-d4) δ ppm 8.01 (s, 1H), 7.88 (d, 1H), 7.78 (s, 1H), 7.76 (s, 1H), 7.16 (d, 1H), 5.16 (m, 1H), 4.29 (m, 2H), 3.99 (s, 3H), 3.82 (m, 2H), 2.17 (s, 3H), 1.95 (d, 3H). LCMS (method B): [MH]+=415.0, tR=2.64 min. Chiral separation (method G) provided enantiomeric pure compounds example 51-R and example 51-S.

Workup

  1. customSolvent was evaporated
  2. customthe residue was partitioned between water and EtOAc
  3. extractionAqueous layer was extracted with EtOAc twice
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customSolvent was evaporated
  7. customthe crude was purified by HPLC (basic with 0.05% NH4OH)

Sources & evidence

ORD record
ord-14c5a5985fb0405bb2bc9230d09e24d0
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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