Cesium carbonate → HCID 90052403, compound

HRID 2284779Notes

Reaction equation

HRID 2284779 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([C:14]#[C:15][C:16]2[CH:17]=[C:18]([NH:22][C:23](=[O:35])[C@@H:24]([N:26]([CH3:34])[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH3:25])[CH:19]=[CH:20][CH:21]=2)=[CH:4][N:3]=1.[NH2:36][CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=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].O1CCOCC1>[CH3:34][N:26]([C@@H:24]([CH3:25])[C:23]([NH:22][C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([C:15]#[C:14][C:5]2[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[N:7][C:2]([NH:36][CH2:37][CH2:38][C:39]3[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=3)=[N:3][CH:4]=2)[CH:17]=1)=[O:35])[C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 832754-PyridineethanamineHCID 90052476HCID 90052476, compound

Product 1

HCID 90052403HCID 90052403, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To (S)-tert-butyl (1-((3-((2-chloro-4-morpholinopyrimidin-5-yl)ethynyl)phenyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (L5, 437 mg), 4-(2-aminoethyl)pyridine (214 mg), tris(dibenzylideneacetone)dipalladium(0) (80 mg), 4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene (101 mg) and cesium carbonate (856 mg), 1,4-dioxane (10 mL) was added at room temperature, and the mixture was stirred at 100° C. for 12 hours. The reaction mixture was cooled to room temperature, then the insoluble matter was removed by filtration through Cerite, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 95% ethyl acetate/5% methanol) to obtain (S)-tert-butyl methyl(1-((3-((4-morpholino-2-((2-(pyridin-4-yl)ethyl)amino)pyrimidin-5-yl)ethynyl)phenyl)amino)-1-oxopropan-2-yl)carbamate (L6, 104 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customthe insoluble matter was removed by filtration through Cerite
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (eluent, 95% ethyl acetate/5% methanol)

Sources & evidence

ORD record
ord-3f4047c9059f47eaade33f865228edb5
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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