Pyridine → 2-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]-triazolo[4,3-b]pyridazin-3-yl)propan-2-yl acetate

HRID 1930066Notes

Reaction equation

HRID 1930066 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[CH:19][C:20]3[N:21]([C:23]([C:26]([OH:29])([CH3:28])[CH3:27])=[N:24][N:25]=3)[N:22]=1)[CH:14]=[CH:13][O:12]2.N1C=CC=CC=1.[C:36](OC(=O)C)(=[O:38])[CH3:37].C(Cl)(=O)C>CN(C=O)C.C(Cl)Cl>[C:36]([O:29][C:26]([C:23]1[N:21]2[N:22]=[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]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])[CH:18]=[CH:19][C:20]2=[N:25][N:24]=1)([CH3:27])[CH3:28])(=[O:38])[CH3:37]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 6367Acetyl chloride2×HCID 7918Acetic AnhydrideHCID 251678402-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)propan-2-ol

Product 1

HCID 579299772-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]-triazolo[4,3-b]pyridazin-3-yl)propan-2-yl acetateYield 54.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

2-(6-(6-(2,4-Difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)propan-2-ol (0.125 g, 0.315 mmol, Example #37) was added to DCM (2 mL). Pyridine (0.077 mL, 0.95 mmol) and acetic anhydride (0.045 mL, 0.47 mmol) were added and the suspension was stirred at ambient temperature for about 15 min. Acetyl chloride (0.027 mL, 0.38 mmol) was added and the mixture was stirred at ambient temperature for about 30 min. DMF (1 mL), pyridine (0.077 mL, 0.95 mmol) and acetyl chloride (0.027 mL, 0.38 mmol) were added then the mixture was heated at about 85° C. for about 90 min. The mixture was cooled to ambient temperature, concentrated under reduced pressure then purified by RP-HPLC (Table 1, Method f). Concentration under reduced pressure resulted in a precipitate that was collected by filtration and dried to give the title compound (0.075 g, 54%): LC/MS (Table 1, Method g) Rt=1.96 min; MS m/z: 438.9 (M+H)+.

Workup

  1. stirringthe mixture was stirred at ambient temperature for about 30 min
  2. temperaturethe mixture was heated at about 85° C. for about 90 min
  3. temperatureThe mixture was cooled to ambient temperature
  4. concentrationconcentrated under reduced pressure
  5. customthen purified by RP-HPLC (Table 1, Method f)
  6. concentrationConcentration under reduced pressure
  7. customresulted in a precipitate that
  8. filtrationwas collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-426b4c8e47cc4241a9a5bd53d86e05c2
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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