Cesium carbonate → HCID 86671404, compound

HRID 2403310Notes

Reaction equation

HRID 2403310 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][C:3]=1[CH3:21].Br[C:23]1[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[Br:29][C:26]1[CH:27]=[CH:28][C:23]([NH:1][C:2]2[N:7]=[CH:6][C:5]([CH:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:9]3)=[CH:4][C:3]=2[CH3:21])=[N:24][CH:25]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 693532,5-DibromopyridineHCID 68356521HCID 68356521, compound

Product 1

HCID 86671404HCID 86671404, compoundYield 28.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl (RS)-2-(6-amino-5-methylpyridin-3-yl)morpholine-4-carboxylate (60 mg), 2,5-dibromopyridine (72.7 mg, CAS 624-28-2) and cesium carbonate (100 mg) were combined with dioxane (2 ml) to give a yellow suspension. The mixture was degassed by bubbling argon into the mixture for several minutes. Xantphos (14.1 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (12.6 mg) were then added. The reaction mixture was then capped and stirred at 100° C. overnight and then at 120° C. for 2 hours. The crude reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography (silica gel; gradient: 0% to 100% EtOAc in hexanes) to afford tert-butyl (RS)-2-(6-(5-bromopyridin-2-ylamino)-5-methylpyridin-3-yl)morpholine-4-carboxylate (26 mg, 28%) as a yellow amorphous solid. MS (ISP): 451.1 ([{81Br}M+H]+), 449.1 ([{79Br}M+H]+).

Workup

  1. customto give a yellow suspension
  2. customThe mixture was degassed
  3. customby bubbling argon into the mixture for several minutes
  4. additionXantphos (14.1 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (12.6 mg) were then added
  5. customThe reaction mixture was then capped
  6. waitat 120° C. for 2 hours
  7. customThe crude reaction mixture
  8. temperaturewas cooled to room temperature
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customthe residue was purified by flash column chromatography (silica gel; gradient: 0% to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b154bd72c6344985b3106958e68b00f8
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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