Ammonium Chloride → 3-(4-((6-Amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)-1,1-dimethylurea

HRID 626524Notes

Reaction equation

HRID 626524 reaction equation
[CH3:1][N:2]([CH3:23])[C:3]([NH:5][C:6]1[CH:11]=[C:10]([O:12][C:13]2[C:14]([CH3:22])=[N:15][C:16]([N+:19]([O-])=O)=[CH:17][CH:18]=2)[CH:9]=[CH:8][N:7]=1)=[O:4].[NH4+].[Cl-]>CO.C1COCC1.CCOC(C)=O.[Zn]>[NH2:19][C:16]1[N:15]=[C:14]([CH3:22])[C:13]([O:12][C:10]2[CH:9]=[CH:8][N:7]=[C:6]([NH:5][C:3](=[O:4])[N:2]([CH3:23])[CH3:1])[CH:11]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 2

HCID 25517Ammonium Chloride2×HCID 904098671,1-Dimethyl-3-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea

Product 1

HCID 904098553-(4-((6-Amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)-1,1-dimethylureaYield 96.3%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalyst2×HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1,1-dimethyl-3-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea (5.2 g, 16.4 mmol) in MeOH (60 mL) and THF (60 mL) was treated with NH4Cl (26.3 g, 492 mmol) and stirred vigorously at RT. Zinc dust (10.72 g, 164 mmol) was added portion-wise and the mixture was stirred at RT for 2 h. Additional portions of NH4Cl (5 g, 93 mmol) and zinc dust (1 g, 15 mmol) were added and stirring was continued overnight. The mixture was diluted with EtOAc and filtered. The filtered solids were washed with EtOAc. The combined filtrates were further filtered (2×) and concentrated to dryness. THF (150 mL) and thiol-modified silica gel (1.4 mmol/g loading, 22 g, 31 mmol) were added and the mixture was stirred at RT overnight. The solids were removed by filtration and washed with THF. The combined filtrates were concentrated to dryness to give 3-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)-1,1-dimethylurea (4.54 g, 96%) as a foam. MS (ESI) m/z: 288.1 (M+H+).

Workup

  1. stirringthe mixture was stirred at RT for 2 h
  2. stirringstirring
  3. filtrationfiltered
  4. washThe filtered solids were washed with EtOAc
  5. filtrationThe combined filtrates were further filtered (2×)
  6. concentrationconcentrated to dryness
  7. stirringthe mixture was stirred at RT overnight
  8. customThe solids were removed by filtration
  9. washwashed with THF
  10. concentrationThe combined filtrates were concentrated to dryness

Sources & evidence

ORD record
ord-4dfe171ddd974316b5707505a69b9fd1
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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