Diiodomethane → HCID 90427191, compound

HRID 718188Notes

Reaction equation

HRID 718188 reaction equation
[CH3:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[CH:10]=2)=[C:6]([CH3:21])[N:5]=[C:4](N)[CH:3]=1.[I:23]CI.C(ON=O)(C)(C)C>CC#N>[I:23][C:4]1[N:5]=[C:6]([CH3:21])[C:7]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[CH:10]=2)=[C:2]([CH3:1])[CH:3]=1

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 10906Tert-Butyl nitrite2×HCID 90402691HCID 90402691, compound

Product 1

HCID 90427191HCID 90427191, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4,6-Dimethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (0.41 g, 1.4 mmol), KI (2.30 g, 13.9 mmol), and diiodomethane (4 mL, 49.6 mmol) were combined and stirred at RT. The suspension was treated with tert-butylnitrite (1.0 mL, 8.3 mmol) and the reaction mixture was stirred at RT for 12 h. The mixture was diluted with MeCN (10 mL), additional tert-butylnitrite (1.0 mL, 8.3 mmol) was added and stirring was continued at RT for 24 h. The reaction mixture was partitioned between EtOAc (120 mL) and sat. NaHCO3 (aq) (20 mL). The aqueous phase was collected and the organic phase was washed with sat. NaHCO3 (aq) (2×20 mL), 10% Na2S2O3(aq) (2×20 mL), and brine (2×20 mL). The combined aqueous washes were back-extracted with EtOAc (2×20 mL) and the combined organics were dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (EtOAc/DCM) to afford 6-iodo-2,4-dimethyl-3-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridine (0.24 g, 43%) as an off white solid that was used in the next step without further purification. MS (ESI) m/z: 407.0 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred at RT for 12 h
  2. additionwas added
  3. stirringstirring
  4. customThe reaction mixture was partitioned between EtOAc (120 mL) and sat. NaHCO3 (aq) (20 mL)
  5. customThe aqueous phase was collected
  6. washthe organic phase was washed with sat. NaHCO3 (aq) (2×20 mL), 10% Na2S2O3(aq) (2×20 mL), and brine (2×20 mL)
  7. extractionThe combined aqueous washes were back-extracted with EtOAc (2×20 mL)
  8. dry with materialthe combined organics were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record
ord-fb5df84560864060a2b94f77f63069f7
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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