Cesium carbonate → (S)-tert-butyl methyl(1-((5-(2-((2-methylpyridin-4-yl)amino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)carbamate

HRID 2284823Notes

Reaction equation

HRID 2284823 reaction equation
C1(P(C2CCCCC2)C2C(OC)=CC=C(OC)C=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Cl[C:40]1[N:45]=[C:44]([NH:46][CH2:47][CH2:48][CH3:49])[C:43]([C:50]#[C:51][CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:68])[C@@H:57]([N:59]([CH3:67])[C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:64])[CH3:63])[CH3:58])=[CH:42][N:41]=1.[CH3:69][C:70]1[CH:75]=[C:74]([NH2:76])[CH:73]=[CH:72][N:71]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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>[CH3:67][N:59]([C@@H:57]([CH3:58])[C:56]([NH:55][CH2:54][CH2:53][CH2:52][C:51]#[C:50][C:43]1[C:44]([NH:46][CH2:47][CH2:48][CH3:49])=[N:45][C:40]([NH:76][C:74]2[CH:73]=[CH:72][N:71]=[C:70]([CH3:69])[CH:75]=2)=[N:41][CH:42]=1)=[O:68])[C:60](=[O:66])[O:61][C:62]([CH3:65])([CH3:64])[CH3:63]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 7286704-Amino-2-methylpyridineHCID 25112535BrettphosHCID 90052304(S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Product 1

HCID 90052580(S)-tert-butyl methyl(1-((5-(2-((2-methylpyridin-4-yl)amino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)carbamateYield 38.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a solution of tris(dibenzylideneacetone)dipalladium(0) (1.0 mg) in 1,4-dioxane (0.86 mL), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl (1.5 mg) was added at room temperature under a nitrogen atmosphere, and the mixture was stirred at 100° C. for 5 minutes. The reaction mixture was cooled to room temperature, and then (S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (V1, 12.5 mg), 2-methyl-4-aminopyridine (4.0 mg) and cesium carbonate (19 mg) were added, and the mixture was stirred at 70° C. for 1 hour. The reaction mixture was cooled to room temperature, and then ethyl acetate was added to the reaction mixture. 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, 80 to 0% hexane in ethyl acetate) to obtain (S)-tert-butyl methyl(1-((5-(2-((2-methylpyridin-4-yl)amino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)carbamate (V2, 5.6 mg) as yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred at 70° C. for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe insoluble matter was removed by filtration through Cerite
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 80 to 0% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-6b5a123578ad4b698769e88306333db3
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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