Cesium carbonate → HCID 86683894, compound

HRID 340515Notes

Reaction equation

HRID 340515 reaction equation
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.[NH2:43][C:44]1[N:49]=[C:48]([NH:50][C@H:51]2[CH2:56][CH2:55][CH2:54][CH2:53][C@H:52]2[NH:57][C:58](=[O:64])[O:59][C:60]([CH3:63])([CH3:62])[CH3:61])[C:47]([Cl:65])=[CH:46][C:45]=1[C:66]([NH:68][C:69]([C:72]1[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=1)([CH3:71])[CH3:70])=[O:67].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:85]1[CH:86]=[N:87][CH:88]=[C:89]([CH3:91])[CH:90]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O.O1CCOCC1>[Cl:65][C:47]1[C:48]([NH:50][C@H:51]2[CH2:56][CH2:55][CH2:54][CH2:53][C@H:52]2[NH:57][C:58](=[O:64])[O:59][C:60]([CH3:63])([CH3:61])[CH3:62])=[N:49][C:44]([NH:43][C:85]2[CH:86]=[N:87][CH:88]=[C:89]([CH3:91])[CH:90]=2)=[C:45]([C:66]([NH:68][C:69]([C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)([CH3:70])[CH3:71])=[O:67])[CH:46]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 8177133-Bromo-5-methylpyridineHCID 86683895HCID 86683895, compound

Product 1

HCID 86683894HCID 86683894, compoundYield 55%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Xantphos (5 mg) and Pd2(dba)3 (4 mg) were added to a mixture of tert-butyl cis-2-(6-amino-3-chloro-5-(2-phenylpropan-2-ylaminocarbonyl)pyridin-2-ylamino)cyclohexylcarbamate (20 mg), cesium carbonate (20 mg), 3-bromo-5-methylpyridine (9 mg), and 1,4-dioxane (2 ml) in a nitrogen atmosphere, followed by reflux for 3 hours in a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. The organic layer was collected, washed with saturated saline, and dried over anhydrous sodium sulfate, and the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel chromatography (silica gel: Kanto Chemical Co., Inc., silica gel 60 (spherical shape), hexane•ethyl acetate=2:1 to 3:1), and a white solid of tert-butyl cis-2-(3-chloro-5-(2-phenylpropan-2-ylaminocarbonyl)-6-(5-methylpyridin-3-ylamino)pyridin-2-ylamino)cyclohexylcarbamate (13 mg) was thus obtained.

Workup

  1. temperatureby reflux for 3 hours in a nitrogen atmosphere
  2. customThe organic layer was collected
  3. washwashed with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled away under reduced pressure
  6. customThe obtained residue was purified by silica gel chromatography (silica gel: Kanto Chemical Co., Inc., silica gel 60 (spherical shape), hexane•ethyl acetate=2:1 to 3:1)

Sources & evidence

ORD record
ord-05ac3797aea743949348f0f8497200f5
Source dataset
uspto-grants-2014_11
Patent number
US08895585B2

Reaction notes

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