Stannous Chloride → 5-((2-(4-(1-Methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-amine

HRID 1049340Notes

Reaction equation

HRID 1049340 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[C:18]([O:20][C:21]4[CH:22]=[N:23][C:24]([N+:27]([O-])=O)=[CH:25][CH:26]=4)[CH:17]=[CH:16][N:15]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[Sn](Cl)Cl>CCOC(C)=O.CCO>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:19]=[C:18]([O:20][C:21]4[CH:26]=[CH:25][C:24]([NH2:27])=[N:23][CH:22]=4)[CH:17]=[CH:16][N:15]=3)=[CH:12][CH:13]=2)[CH2:6][CH2:7]1

Participants

5

Reactant 2

HCID 24479Stannous Chloride4×HCID 904036432-(4-(1-Methylpiperidin-4-yl)phenyl)-4-((6-nitropyridin-3-yl)oxy)pyridine

Product 1

HCID 904033245-((2-(4-(1-Methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-amineYield 136%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 2-(4-(1-methylpiperidin-4-yl)phenyl)-4-((6-nitropyridin-3-yl)oxy)pyridine (0.199 g, 0.510 mmol) in EtOAc (10 mL) and EtOH (10 mL) was treated with tin(II) chloride dehydrate (0.575 g, 2.55 mmol), heated at 65° C. for 4 h, then heated 75° C. overnight. Additional tin(II) chloride dehydrate (300 mg) was added, the mixture heated at 80° C. for 6 h, treated with another portion of tin(II) chloride dehydrate (300 mg) and heated at 80° C. for 3 days. Additional tin(II) chloride dehydrate (300 mg) was added and the mixture heated at 80° C. overnight. The mixture was cooled to RT, concentrated to dryness, treated with EtOAc and satd. NaHCO3, filtered through diatomaceous earth and the filter cake rinsed with EtOAc/THF. The filtrate was treated with solid NaOH (2 g) and NaCl until the aqueous layer was saturated, extracted with 3:1 EtOAc/THF (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford 5-((2-(4-(1-methylpiperidin-4-yl)phenyl)pyridin-4-yl)oxy)pyridin-2-amine (250 mg, >100%). MS (ESI) m/z: 361.2 (M+H+).

Workup

  1. temperatureheated 75° C. overnight
  2. temperaturethe mixture heated at 80° C. for 6 h
  3. temperatureheated at 80° C. for 3 days
  4. temperaturethe mixture heated at 80° C. overnight
  5. temperatureThe mixture was cooled to RT
  6. concentrationconcentrated to dryness
  7. additiontreated with EtOAc and satd
  8. filtrationNaHCO3, filtered through diatomaceous earth
  9. washthe filter cake rinsed with EtOAc/THF
  10. additionThe filtrate was treated with solid NaOH (2 g) and NaCl until the aqueous layer
  11. extractionextracted with 3:1 EtOAc/THF (2×)
  12. washthe combined organics were washed with brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-bb03855592cb4880b9da629737c66184
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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