3-Hydroxy-3-methyl-butanal → 1-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-2-methylpropan-2-ol

HRID 1930095Notes

Reaction equation

HRID 1930095 reaction equation
[OH:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH:4]=O.[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:17]=[C:18]2[N:22]([C:23]=1[C:24]1[N:25]=[N:26][C:27]([NH:30][NH2:31])=[CH:28][CH:29]=1)[CH:21]=[CH:20][O:19]2.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(Cl)Cl>[F:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[C:16]1[N:17]=[C:18]2[N:22]([C:23]=1[C:24]1[CH:29]=[CH:28][C:27]3[N:26]([C:4]([CH2:3][C:2]([CH3:7])([OH:1])[CH3:6])=[N:31][N:30]=3)[N:25]=1)[CH:21]=[CH:20][O:19]2

Participants

5

Reactant 3

HCID 110515913-Hydroxy-3-methyl-butanalHCID 12217721Iodo benzene diacetateHCID 579298696-(2,4-Difluorophenyl)-5-(6-hydrazinylpyridazin-3-yl)imidazo[2,1-b]oxazole

Product 1

HCID 498308011-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-2-methylpropan-2-olYield 33.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To round bottom flask, 3-hydroxy-3-methylbutanal (0.178 g, 1.185 mmol) and 6-(2,4-difluorophenyl)-5-(6-hydrazinylpyridazin-3-yl)imidazo[2,1-b]oxazole (0.3 g, 0.859 mmol) and DCM 5 mL were added. The reaction mixture was stirred at about ambient temperature for about 1 h. Iodobenzene diacetate (0.38 g, 1.18 mmol) was added and was stirred at ambient temperature for overnight. The reaction mixture was quenched with water. The aqueous phase was extracted with DCM and the organic layer was concentrated under reduced pressure. The crude material was purified by silica gel chromatography using DCM/MeOH (90:10). After concentration of the fractions with product, the resulting solid was triturated with ether. The solid was collected by filtration then dried under vacuum at about 60° C. for about 2 days to give the title compound (0.118 g, 33.5%): LC/MS (Table 1, Method g) Rt=1.78 min; MS m/z: 411.2 (M+H)+. 1H NMR (DMSO-d6) δ 8.52 (d, 1H), 8.27 (d, 1H), 8.21 (d, 1H), 7.75 (m, 1H), 7.50-7.40 (m, 1H), 7.34-7.25 (m, 1H), 6.90 (m, 1H), 4.71 (s, 1H), 3.33 (s, 2H), 1.27 (s, 6H)

Workup

  1. stirringwas stirred at ambient temperature for overnight
  2. customThe reaction mixture was quenched with water
  3. extractionThe aqueous phase was extracted with DCM
  4. concentrationthe organic layer was concentrated under reduced pressure
  5. customThe crude material was purified by silica gel chromatography
  6. customAfter concentration of the fractions with product, the resulting solid was triturated with ether
  7. filtrationThe solid was collected by filtration
  8. customthen dried under vacuum at about 60° C. for about 2 days

Sources & evidence

ORD record
ord-23f8338d970d4a7285caf64f16efb392
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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