Acetic Acid → HCID 67983117, compound

HRID 539785Notes

Reaction equation

HRID 539785 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]2[N:12]([CH:14]=[C:15]([C:17]3[CH:18]=[N:19][C:20]([CH3:26])=[C:21]([N+:23]([O-])=O)[CH:22]=3)[N:16]=2)[N:13]=1.CC(O)=O.N1C=CC=CC=1.[CH3:37][C:38]([CH3:43])([CH3:42])[C:39](Cl)=[O:40]>C(O)C.O.[Fe]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]2[N:12]([CH:14]=[C:15]([C:17]3[CH:22]=[C:21]([NH:23][C:39](=[O:40])[C:38]([CH3:43])([CH3:42])[CH3:37])[C:20]([CH3:26])=[N:19][CH:18]=3)[N:16]=2)[N:13]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 1049PyridineHCID 62493Pivaloyl chlorideHCID 68089037HCID 68089037, compound

Product 1

HCID 67983117HCID 67983117, compoundYield 44%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-(2-fluorophenyl)-2-(6-methyl-5-nitropyridin-3-yl)imidazo[1,2-b]pyridazine (0.016 g, 0.0458 mmol) in ethanol (3 mL) and water (1 mL) containing AcOH (0.274 mmol) is added iron (0.013 g, 0.229 mmol). The mixture is heated at 80° C. for 2 hours. The mixture is concentrated under reduced pressure and sat. aqueous NaHCO3 (10 mL) is added. The mixture is extracted with EtOAc (20 mL). Organic layer is collected and concentrated to dryness. Crude amine is taken up in acetonitrile (3 mL) containing pyridine (0.137 mmol). To this solution is added trimethylacetylchloride (0.0503 mmol). The mixture is stirred at room temperature for 4 hours, concentrated to dryness and then purified via silica chromatography using a gradient CH2Cl2 to CH2Cl2:EtOAc:methanol (1:1:0.1) to afford the title compound (0.008 g, 44%) as a light yellow solid: Rf 0.34 (1:1:0.1 CH2Cl2:EtOAc:methanol); LCMS (m/z)=404.4 [M+H]+, tR=2.11 min. (compound same as Example 390)

Workup

  1. concentrationThe mixture is concentrated under reduced pressure and sat. aqueous NaHCO3 (10 mL)
  2. additionis added
  3. extractionThe mixture is extracted with EtOAc (20 mL)
  4. customOrganic layer is collected
  5. concentrationconcentrated to dryness
  6. concentrationconcentrated to dryness
  7. custompurified via silica chromatography

Sources & evidence

ORD record
ord-64ab6fec4fff447c915b59735e5404c0
Source dataset
uspto-grants-2014_10
Patent number
US08871767B2

Reaction notes

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