Tributylstannane → 2-Fluoro-5-[(6-methyl-3-pyridinyl)oxy]benzenamine

HRID 2042040Notes

Reaction equation

HRID 2042040 reaction equation
[H-].[Na+].C(=S)=S.CI.C(SC)(=S)O[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[C:20]([NH2:25])[CH:19]=2)=[CH:13][N:12]=1.C([SnH](CCCC)CCCC)CCC.CC(N=NC(C#N)(C)C)(C#N)C>C1COCC1.C1(C)C=CC=CC=1>[F:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][C:14]2[CH:13]=[N:12][C:11]([CH3:10])=[CH:16][CH:15]=2)=[CH:19][C:20]=1[NH2:25]

Participants

9

Reactant 6

HCID 5948TributylstannaneHCID 6328Methyl iodideHCID 6348Carbon DisulfideHCID 6547AzobisisobutyronitrileHCID 24758Sodium hydrideHCID 86619669O-[[5-(3-Amino-4-fluorophenoxy)-2-pyridinyl]methyl] S-methyl carbonodithioate

Product 1

HCID 672522792-Fluoro-5-[(6-methyl-3-pyridinyl)oxy]benzenamineYield 56.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

NaH (100 mg, 3.3 mmol) was slowly added to a solution of Example A12 (0.50 g, 2.1 mmol) in dry THF (50 mL) at 0° C. After 30 min, CS2 (0.49 g, 6.4 mmol) was added and the reaction mixture was stirred at 0° C. for 1 hour. Methyl iodide (2.4 g, 17 mmol) was added at 0° C. and the reaction mixture was allowed to warm to RT overnight. The solvent was removed under reduced pressure to obtain the crude product. The crude, O-(5-(3-amino-4-fluorophenoxy)pyridin-2-yl)methyl S-methyl carbonodithioate (0.69 g, 2.1 mmol) was dissolved in toluene (5 mL) and tributyltin hydride (1 mL) and AIBN (50 mg) were added. The reaction mixture was heated under reflux for 3 hours. The solvent was removed under reduced pressure and the residue was filtered and washed with CH2Cl2. The filtrate was evaporated and the residue was purified by silica gel column chromatography to obtain 2-fluoro-5-(6-methylpyridin-3-yloxy)benzenamine (0.26 g, 56% yield). 1H NMR (400 MHz, DMSO-d6) δ 8.20 (d, J=2.8 Hz, 1H), 7.30 (dd, J=2.8, and 8.4 Hz, 1H), 7.25 (d, J=8.4 Hz, 1H), 6.97 (dd, J=8.8, 11.6 Hz, 1H), 6.38 (dd, J=3.2, 7.6 Hz, 1H), 6.13 (dt, J=3.2, 8.8 Hz, 1H), 5.31 (s, 1H), 2.44 (s, 3H); MS (ESI) m/z: 219.0 (M+H+).

Workup

  1. temperatureto warm to RT overnight
  2. customThe solvent was removed under reduced pressure
  3. customto obtain the crude product
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for 3 hours
  6. customThe solvent was removed under reduced pressure
  7. filtrationthe residue was filtered
  8. washwashed with CH2Cl2
  9. customThe filtrate was evaporated
  10. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-aa1895d43a9846929851446f4db398df
Source dataset
uspto-grants-2013_11
Patent number
US08586565B2

Reaction notes

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