Potassium Carbonate → (3R)-3-ethyl-1-(2-((2-methyl-1,3-thiazol-5-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile hydrochloride

HRID 714888ノート

反応式

HRID 714888 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH2:15][CH3:16])([C:13]#[N:14])[C:9]2=[O:17])[CH:5]=[CH:4][N:3]=1.[CH3:18][C:19]1[S:20][C:21]([NH2:24])=[CH:22][N:23]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C(O)(C)(C)C.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]>[ClH:1].[CH2:15]([C@:10]1([C:13]#[N:14])[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:24][C:21]3[S:20][C:19]([CH3:18])=[N:23][CH:22]=3)[N:7]=2)[C:9]1=[O:17])[CH3:16]

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 208298802-Methyl-1,3-thiazol-5-amineHCID 117840665(3R)-1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile

生成物 1

HCID 117840893(3R)-3-ethyl-1-(2-((2-methyl-1,3-thiazol-5-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile hydrochloride収率 10.3%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6386tert-Butanol溶媒

実験手順

To a mixture of (3R)-1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile (100 mg) obtained in Step A of Example 8, 2-methyl-1,3-thiazol-5-amine (56 mg), potassium carbonate (110 mg) and dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (58 mg) in tert-butanol (1.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (22 mg), and the mixture was stirred for 5 hr with heated under reflux. The insoluble substance was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the obtained compound (26 mg) in ethanol (2.0 mL) was added 1 M hydrochloric acid (80 μL), and the mixture was stirred at room temperature for 5 min. The solvent was evaporated under reduced pressure, and the residue was recrystallized (ethanol) to give the title compound (15 mg).

後処理

  1. temperaturewith heated
  2. temperatureunder reflux
  3. customThe insoluble substance was removed by filtration through Celite
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  6. additionTo a solution of the obtained compound (26 mg) in ethanol (2.0 mL) was added 1 M hydrochloric acid (80 μL)
  7. stirringthe mixture was stirred at room temperature for 5 min
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was recrystallized (ethanol)

出典と根拠

ORDレコード
ord-1d052eeb7c8e491db6e905342eba5eea
出典データセット
uspto-grants-2015_11
特許番号
US09187453B2

反応ノート

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