Cesium carbonate → HCID 86671407, compound

HRID 2403319Notes

Reaction equation

HRID 2403319 reaction equation
[NH2:1][C:2]1[CH: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[Cl:21].Cl[C:23]1[N:28]=[CH:27][C:26]([CH:29]2[CH2:31][CH2:30]2)=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[Cl:21][C:3]1[CH:4]=[C:5]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:18])([CH3:20])[CH3:19])=[O:15])[CH2:9]2)[CH:6]=[CH:7][C:2]=1[NH:1][C:23]1[N:28]=[CH:27][C:26]([CH:29]2[CH2:31][CH2:30]2)=[CH:25][N:24]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 468640872-Chloro-5-cyclopropylpyrimidineHCID 68325445HCID 68325445, compound

Product 1

HCID 86671407HCID 86671407, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

tert-Butyl (RS)-2-(4-amino-3-chlorophenyl)morpholine-4-carboxylate (70 mg), 2-chloro-5-cyclopropylpyrimidine (45.0 mg, CAS 166740-44-9) and cesium carbonate (109 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 (7.77 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (6.95 mg) were then added. The reaction mixture was then capped and stirred at 120° C. for 16 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 75% EtOAc in hexanes) to afford tert-butyl (RS)-2-(3-chloro-4-(5-cyclopropylpyrimidin-2-ylamino)phenyl)morpholine-4-carboxylate (48 mg, 50%) as a colourless amorphous solid. MS (ISP): 433.2 ([{37Cl}M+H]+), 431.2 ([{35Cl}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 (7.77 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (6.95 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 75% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9de7ee60b3954008909bd1fc2c23cac6
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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