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 2284823노트

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HRID 2284823 반응식
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]

참가 물질

8

반응물 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

생성물 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)carbamate수율 38.5%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-6b5a123578ad4b698769e88306333db3
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09145415B2

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