Cesium carbonate → HCID 86671398, compound

HRID 2403301Notes

Reaction equation

HRID 2403301 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:21])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:23]1[N:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[Cl:29][C:26]1[CH:25]=[N:24][C:23]([NH:20][C:17]2[CH:18]=[CH:19][C:14]([CH:10]3[O:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]3)=[CH:15][C:16]=2[F:21])=[N:28][CH:27]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5906412,5-DichloropyrimidineHCID 68325450Tert-butyl 2-(4-amino-3-fluorophenyl)morpholine-4-carboxylate

Product 1

HCID 86671398HCID 86671398, compoundYield 31.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

(RS)-2-(4-Amino-3-fluoro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (60 mg), 2,5-dichloropyrimidine (30.2 mg, CAS 22536-67-0) and cesium carbonate (99 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 (7.03 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (6.29 mg) were then added. The reaction mixture was then capped and stirred 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 80% EtOAc in hexanes) to afford tert-butyl (RS)-2-(4-(5-chloropyrimidin-2-ylamino)-3-fluorophenyl)morpholine-4-carboxylate (26 mg, 31%) as a colourless amorphous solid. MS (ISP): 411.3 ([{37Cl}M+H]+), 409.2 ([{35Cl}M+H]+), 355.3 ([{37Cl}M+H—C4H8]+), 353.3 ([{35Cl}M+H—C4H8]+).

Workup

  1. customto give a yellow suspension
  2. customThe mixture was degassed
  3. customby bubbling argon into the mixture for several minutes
  4. additionXantphos (7.03 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (6.29 mg) were then added
  5. customThe reaction mixture was then capped
  6. customThe crude reaction mixture
  7. temperaturewas cooled to room temperature
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by flash column chromatography (silica gel; gradient: 0% to 80% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ea71473424d0463ba04a989b74c998cd
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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