Diiodomethane → 2-Iodo-4-methyl-5-[[2-(1-methyl-1H-pyrazol-4-yl)-4-pyridinyl]oxy]pyridine

HRID 709963Notes

Reaction equation

HRID 709963 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)=[CH:6][N:5]=[C:4](N)[CH:3]=1.[I:22]CI.C(ON=O)(C)(C)C>CCOC(C)=O>[I:22][C:4]1[CH:3]=[C:2]([CH3:1])[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)=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 10906Tert-Butyl nitriteHCID 686640964-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine

Product 1

HCID 904160832-Iodo-4-methyl-5-[[2-(1-methyl-1H-pyrazol-4-yl)-4-pyridinyl]oxy]pyridineYield 59.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of Example A2 (0.62 g, 2.2 mmol), KI (3.7 g, 22.3 mmol), and diiodomethane (5 mL, 62 mmol) was treated with t-butylnitrite (1.4 mL, 11.7 mmol) and stirred at RT for 12 h. The mixture was treated with EtOAc, washed successively with satd. NaHCO3 (3×), 10% Na2S2O3 (2×), and brine (2×) and the combined aqueous washes were back-extracted with EtOAc (2×). The combined organics were dried over MgSO4, concentrated to dryness and purified by silica gel chromatography (EtOAc/DCM) to afford 2-iodo-4-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridine (0.51 g, 59%). MS (ESI) m/z: 393.0 (M+H+).

Workup

  1. washwashed successively with satd
  2. extractionNaHCO3 (3×), 10% Na2S2O3 (2×), and brine (2×) and the combined aqueous washes were back-extracted with EtOAc (2×)
  3. dry with materialThe combined organics were dried over MgSO4
  4. concentrationconcentrated to dryness
  5. custompurified by silica gel chromatography (EtOAc/DCM)

Sources & evidence

ORD record
ord-19af7185588e4748bfa217122e6e7ea7
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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