Pivalaldehyde → HCID 57929939, compound

HRID 1929976Notes

Reaction equation

HRID 1929976 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[N:18]=[N:19][C:20]([NH:23][NH2:24])=[CH:21][CH:22]=1)[CH:14]=[CH:13][O:12]2.F[C:26]1C=CC(F)=[CH:28][C:27]=1[C:33](=O)C.O1C=CN=[C:37]1N.C1C(=O)N(I)C(=O)C1.ClN1C=CC(I)=CN1.O.NN.CC(C)(C)C=O.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(O)(=O)C.C(Cl)Cl.CO>[C:27]([C:33]1[N:19]2[N:18]=[C:17]([C:16]3[N:15]4[C:11]([O:12][CH:13]=[CH:14]4)=[N:10][C:9]=3[C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[F:1])[CH:22]=[CH:21][C:20]2=[N:23][N:24]=1)([CH3:37])([CH3:28])[CH3:26]

Participants

12

Reactant 8

HCID 12417PivalaldehydeHCID 24654Hydrazine hydrate (1:1)HCID 747941-(2,5-Difluorophenyl)ethan-1-oneHCID 120273N-IodosuccinimideHCID 5585212-AminooxazoleHCID 12217721Iodo benzene diacetateHCID 57929877HCID 57929877, compoundHCID 86635298HCID 86635298, compound

Product 1

HCID 57929939HCID 57929939, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 6-(2,5-difluorophenyl)-5-(6-hydrazinylpyridazin-3-yl)imidazo[2,1-b]oxazole (0.30 g, 0.84 mmol; (prepared using General Procedure A.1 from 1-(2,5-difluorophenyl)ethanone [Matrix], General Procedure B from oxazole-2-amine [GL Synthesis], General Procedure C with NIS, General Procedure I from 1-chloro-4-iodopyridazine (prepared using General Procedure H from 3,6-dichloropyridazine), and General Procedure D with hydrazine hydrate), trimethylacetaldehyde (0.076 g, 0.88 mmol), and glacial acetic acid (1 drop) was dissolved in DCM (6 mL) and MeOH (1 mL) and stirred at ambient temperature for about 1 h. Iodobenzene diacetate (0.28 g, 0.88 mmol) was added and was stirred for about 1 h at ambient temperature. The reaction was diluted with DCM (75 mL) and washed with saturated Na2CO3 solution (150 mL) and water (100 mL). The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography using DCM/MeOH (gradient, 97:3 to 90:10). After concentration of the clean fractions, the resulting cream solid was solubilized in hot MeOH, sonicated while cooling, and concentrated under reduced pressure. The resulting solid was dried in a vacuum oven at about 70° C. overnight to provide the title compound as a cream solid (0.22 g, 66%): LC/MS (Table 1, Method a) Rt=2.37 min; MS m/z: 395.2 (M+H)+.

Workup

  1. washwashed with saturated Na2CO3 solution (150 mL) and water (100 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by silica gel chromatography
  6. customsonicated
  7. temperaturewhile cooling
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting solid was dried in a vacuum oven at about 70° C. overnight

Sources & evidence

ORD record
ord-d797f69814b74d52b854d078ff2caa40
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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