Ammonium Chloride → 5-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

HRID 1049230Notes

Reaction equation

HRID 1049230 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[C:11]([O:13][C:14]3[CH:15]=[N:16][C:17]([N+:20]([O-])=O)=[CH:18][CH:19]=3)[CH:10]=[CH:9][N:8]=2)[CH:4]=[N:3]1.[NH4+].[Cl-]>CCO.O.[Fe]>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[C:11]([O:13][C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[N:16][CH:15]=3)[CH:10]=[CH:9][N:8]=2)[CH:4]=[N:3]1

Participants

6

Reactant 2

HCID 25517Ammonium Chloride2×HCID 904029412-(1-Methyl-1h-pyrazol-4-yl)-4-[(6-nitro-3-pyridinyl)oxy]pyridine

Product 1

HCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amineYield 60%

Reagents, catalysts & solvents 3

HCID 23925IronCatalyst2×HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 2-(1-methyl-1H-pyrazol-4-yl)-4-((6-nitropyridin-3-yl)oxy)pyridine (11.88 g, 40.0 mmol) and NH4Cl (22.4 g, 419 mmol) in EtOH (200 mL) and water (200 mL) was treated portion-wise with iron powder (22.4 g, 401 mmol), stirred for 0.5 h, treated with additional NH4Cl (22.4 g, 419 mmol) and iron powder (22.4 g, 401 mmol) and stirred at RT for 3 h. The solids were removed via filtration through diatomaceous earth and washed with EtOAc and DCM. The filtrate was washed with water, the aqueous layer back-extracted with DCM (4×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (6.4 g, 60%). MS (ESI) m/z: 268.1 (M+H+).

Workup

  1. stirringstirred at RT for 3 h
  2. customThe solids were removed via filtration through diatomaceous earth
  3. washwashed with EtOAc and DCM
  4. washThe filtrate was washed with water
  5. extractionthe aqueous layer back-extracted with DCM (4×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-97a6030a52424912bec2dc1a619a198d
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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