Cesium carbonate → (3S)-3-cyclopropyl-1-(2-((1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

HRID 714843ノート

反応式

HRID 714843 の反応式
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH:15]3[CH2:17][CH2:16]3)([C:13]#[N:14])[C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:21]=[N:22][N:23]([C:25]2([CH2:28][OH:29])[CH2:27][CH2:26]2)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])O.[Na+]>O1CCCC1.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].O.C(#N)C>[CH:15]1([C@:10]2([C:13]#[N:14])[CH2:11][CH2:12][N:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]4[CH:21]=[N:22][N:23]([C:25]5([CH2:28][OH:29])[CH2:26][CH2:27]5)[CH:24]=4)[N:7]=3)[C:9]2=[O:18])[CH2:17][CH2:16]1

参加物

9

反応物 5

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 634876Binap, (A+-)-HCID 91618623(1-(4-amino-1H-pyrazol-1-yl)cyclopropyl)methanolHCID 117840203(3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile

生成物 1

HCID 71766894(3S)-3-cyclopropyl-1-(2-((1-(1-(hydroxymethyl)cyclopropyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile収率 24.6%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒HCID 18373917Acetonitrile--water (1/1)溶媒

反応条件

温度
90 °C

実験手順

To a solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (200 mg) obtained in Step E of Example 103, (1-(4-amino-1H-pyrazol-1-yl)cyclopropyl)methanol (120 mg) obtained in Step C of Example 128, cesium carbonate (500 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (71 mg) in tetrahydrofuran (10 mL) was added tris(dibenzylideneacetone)dipalladium(0) (70 mg), and the mixture was stirred at 90° C. for 10 hr under argon atmosphere. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate). The obtained crude product was subjected to HPLC (C18, mobile phase: water/acetonitrile (containing 5 mM AcONH4), to the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized (ethyl acetate/diisopropyl ether) to give the title compound (71 mg).

後処理

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)
  3. customThe obtained crude product
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was recrystallized (ethyl acetate/diisopropyl ether)

出典と根拠

ORDレコード
ord-3bae1e8940e84fa2856d2f03a3f3b19b
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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