Cesium carbonate → 3-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one

HRID 1021686ノート

反応式

HRID 1021686 の反応式
[NH2:1][C:2]1[CH:13]=[C:5]2[CH2:6][N:7]([C:10](=[O:12])[CH3:11])[CH2:8][CH2:9][N:4]2[N:3]=1.Br[C:15]1[C:16](=[O:23])[N:17]([CH3:22])[CH:18]=[C:19]([Br:21])[CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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].CO.CCOCC.CCOC(C)=O.O>[C:10]([N:7]1[CH2:8][CH2:9][N:4]2[N:3]=[C:2]([NH:1][C:15]3[C:16](=[O:23])[N:17]([CH3:22])[CH:18]=[C:19]([Br:21])[CH:20]=3)[CH:13]=[C:5]2[CH2:6]1)(=[O:12])[CH3:11]

参加物

11

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 580440081-(2-amino-6,7-dihydropyrazolo[1,5-a]pyrazin-5(4H)-yl)ethanone

生成物 1

HCID 580440563-(5-acetyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-5-bromo-1-methylpyridin-2(1H)-one収率 41%

試薬・触媒・溶媒 6

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A sealed tube was equipped with a magnetic stirrer and charged with 125f (860 mg, 4.8 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.8 g, 6.7 mmol), and cesium carbonate (3.4 g, 10.5 mmol) in 1,4-dioxane (67 mL). After bubbling nitrogen through the solution for 30 min, Xantphos (330 mg, 0.6 mmol) and tris(dibenzylideneacetone)dipalladium(0) (300 mg, 0.3 mmol) were added, and the reaction mixture was heated to 100° C. for 16 h. After this time, H2O (50 mL) and EtOAc (50 mL) were added. The aqueous layer was separated and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine (100 mL) and dried over sodium sulfate. The resulting residue was purified by column chromatography eluting with a gradient of CH2Cl2 —60:35:5 CH2Cl2:Et2O:MeOH to afford a 41% yield of 125g (720 mg).

後処理

  1. customA sealed tube was equipped with a magnetic stirrer
  2. customAfter bubbling nitrogen through the solution for 30 min
  3. customThe aqueous layer was separated
  4. extractionextracted with EtOAc (2×50 mL)
  5. washThe combined organic extracts were washed with brine (100 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe resulting residue was purified by column chromatography
  8. washeluting with a gradient of CH2Cl2 —60:35:5 CH2Cl2

出典と根拠

ORDレコード
ord-53f6355cce8c4010ba3377f3512b34e9
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

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