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

HRID 626511Notes

Reaction equation

HRID 626511 reaction equation
[CH3:1][N:2]([CH3:22])[C:3]([NH:5][C:6]1[CH:11]=[C:10]([O:12][C:13]2[CH:14]=[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]=[CH:14][C:13]([O:12][C:10]2[CH:9]=[CH:8][N:7]=[C:6]([NH:5][C:3](=[O:4])[N:2]([CH3:1])[CH3:22])[CH:11]=2)=[CH:18][CH:17]=1

Participants

7

Reactant 2

HCID 25517Ammonium ChlorideHCID 904108451,1-Dimethyl-3-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea

Product 1

HCID 904106873-(4-((6-Aminopyridin-3-yl)oxy)pyridin-2-yl)-1,1-dimethylurea

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1,1-dimethyl-3-(4-((6-nitropyridin-3-yl)oxy)pyridin-2-yl)urea (6.2 g, 20.4 mmol) in MeOH (100 mL) and THF (100 mL) was treated with NH4Cl (332.8 g, 613 mmol) and cooled to 0° C. with stirring. Zinc dust (13.37 g, 204 mmol) was added portion-wise over 10 min and the mixture was stirred overnight as the cooling bath expired. The mixture was diluted with EtOAc and the solids were removed via filtration, and washed with EtOAc. The filtrate was concentrated to dryness, then suspended in EtOAc. The solids were removed by filtration and the filtrate was concentrated to dryness. The resultant brown solid was suspended in MeCN and sonicated for a few minutes. The light brown solid was collected to afford a first crop of 3-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-1,1-dimethylurea. The MeCN filtrate was concentrated to dryness and again suspended in MeCN. The light brown solid was collected and dried to afford a second crop of 3-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-1,1-dimethylurea (5.57 g combined, 100%). 1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.05 (d, J=5.7 Hz, 1H), 7.77 (d, J=2.9 Hz, 1H), 7.33 (d, J=2.4 Hz, 1H), 7.24 (dd, J=8.9, 2.9 Hz, 1H), 6.53-6.49 (m, 2H), 6.00 (br s, 2H), 2.88 (s, 6H); MS (ESI) m/z: 274.1 (M+H+).

Workup

  1. stirringthe mixture was stirred overnight as the cooling bath
  2. customthe solids were removed via filtration
  3. washwashed with EtOAc
  4. concentrationThe filtrate was concentrated to dryness
  5. customThe solids were removed by filtration
  6. concentrationthe filtrate was concentrated to dryness
  7. customsonicated for a few minutes
  8. customThe light brown solid was collected

Sources & evidence

ORD record
ord-eb19c9bb0249447e8ae4170d6d640f36
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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