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 2284823ノート

反応式

HRID 2284823 の反応式
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]

参加物

8

反応物 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

生成物 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)carbamate収率 38.5%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-6b5a123578ad4b698769e88306333db3
出典データセット
uspto-grants-2015_09
特許番号
US09145415B2

反応ノート

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