Cesium carbonate → tert-Butyl 3-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yloxy)azetidine-1-carboxylate

HRID 1021938Notes

Reaction equation

HRID 1021938 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([O:8][CH:9]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]2)=[CH:4][CH:3]=1.Br[C:21]1[C:22](=[O:29])[N:23]([CH3:28])[CH:24]=[C:25]([Br:27])[CH:26]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O1CCOCC1>[Br:27][C:25]1[CH:26]=[C:21]([NH:1][C:2]2[N:7]=[CH:6][C:5]([O:8][CH:9]3[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10]3)=[CH:4][CH:3]=2)[C:22](=[O:29])[N:23]([CH3:28])[CH:24]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 58043889Tert-butyl 3-((6-aminopyridin-3-yl)oxy)azetidine-1-carboxylate

Product 1

HCID 58043697tert-Butyl 3-(6-(5-Bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yloxy)azetidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 206c (950 mg, 3.6 mmol), XantPhos (125 mg, 0.29 mmol), Pd2dba3 (260 mg, 0.29 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.03 g, 3.9 mmol), Cs2CO3 (1.8 g, 7.2 mmol), and 1,4-dioxane (20 mL). The system was evacuated and refilled with N2. It was then heated at reflux for 2 h. After the completion of the reaction, the mixture was filtered off and washed with methanol (100 mL). The combined filtrate was evaporated in vacuo and the residue was purified on reverse-phase Combiflash to afford 206d (1.46 g, 90%). MS-ESI: [M+H]+ 451.

Workup

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. temperatureIt was then heated
  5. temperatureat reflux for 2 h
  6. customAfter the completion of the reaction
  7. filtrationthe mixture was filtered off
  8. washwashed with methanol (100 mL)
  9. customThe combined filtrate was evaporated in vacuo
  10. customthe residue was purified on reverse-phase Combiflash

Sources & evidence

ORD record
ord-b24fabbcc7eb4f98a3b1247212b17962
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

Loading…