Methyl iodide → Tert-butyl 2,6-dichloro-3-(methylamino)pyridin-4-ylcarbamate

HRID 2209014Notes

Reaction equation

HRID 2209014 reaction equation
[CH:1]1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[NH2:35][C:36]1[C:37]([Cl:51])=[N:38][C:39]([Cl:50])=[CH:40][C:41]=1[NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46].C([O-])([O-])=O.[Cs+].[Cs+].CI>C1(C)C=CC=CC=1.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:51][C:37]1[C:36]([NH:35][CH3:1])=[C:41]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:46])([CH3:47])[CH3:48])[CH:40]=[C:39]([Cl:50])[N:38]=1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86724467Tert-butyl (3-amino-2,6-dichloropyridin-4-yl)carbamate

Product 1

HCID 117843103Tert-butyl 2,6-dichloro-3-(methylamino)pyridin-4-ylcarbamate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

Palladium (II) acetate (0.21 g, 0.31 mmol) and 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-phos) (0.36 g, 0.75 mmol) were combined in toluene and heated at 120° C. for 3 min in microwave reactor. To this mixture tert-butyl 3-amino-2,6-dichloropyridin-4-ylcarbamate 2.43 (0.87 g, 3.12 mmol), Cs2CO3 (3.06 g, 9.38 mmol) and methyl iodide (0.196 mL, 3.12 mmol) were added and heated at 90° C. for 2 hr in a microwave reactor. After completion of the reaction, solvent was removed under reduced pressure. Solids were dissolved and extracted with ethyl acetate and water. Organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue obtained was heated in acetonitrile and solids were filtered out to obtain tert-butyl 2,6-dichloro-3-(methylamino)pyridin-4-ylcarbamate 2.44 that was used for next step without further purification.

Workup

  1. temperatureheated at 90° C. for 2 hr in a microwave reactor
  2. customAfter completion of the reaction, solvent
  3. customwas removed under reduced pressure
  4. dissolutionSolids were dissolved
  5. extractionextracted with ethyl acetate and water
  6. washOrganic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue obtained
  11. filtrationsolids were filtered out

Sources & evidence

ORD record
ord-ffea92ef7a3a4e759d2fd9777e5ebe9e
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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