Cesium carbonate → 5-Bromo-3-(5-(2-methoxyethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1,6-dimethylpyridin-2(1H)-one

HRID 593158ノート

反応式

HRID 593158 の反応式
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]2[N:11]=[C:12]([NH2:14])[CH:13]=[C:7]2[CH2:6]1.Br[C:16]1[C:17](=[O:25])[N:18]([CH3:24])[C:19]([CH3:23])=[C:20]([Br:22])[CH:21]=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>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].O1CCOCC1>[Br:22][C:20]1[CH:21]=[C:16]([NH:14][C:12]2[CH:13]=[C:7]3[CH2:6][N:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:10][CH2:9][N:8]3[N:11]=2)[C:17](=[O:25])[N:18]([CH3:24])[C:19]=1[CH3:23]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 299237793,5-Dibromo-1,6-dimethylpyridin-2(1H)-oneHCID 866839915-(2-Methoxyethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

生成物 1

HCID 866845905-Bromo-3-(5-(2-methoxyethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1,6-dimethylpyridin-2(1H)-one収率 62%

試薬・触媒・溶媒 2

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

実験手順

A 100-mL round-bottomed flask equipped with a reflux condenser was charged with 327b (392 mg, 2.0 mmol), 327d (562 mg, 2.0 mmol), cesium carbonate (1.30 g, 4.0 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the suspension for 10 minutes, xantphos (115 mg, 0.20 mmol) and tris(dibenzylideneacetone)dipalladium(0) (92 mg, 0.10 mmol) were added. The system was subjected to three cycles of vacuum/nitrogen flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (2×15 mL). The combined filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (80:1 to 30:1) to afford 327e (490 mg, 62%) as a yellow solid. MS-ESI: [M+H]+ 396.2

後処理

  1. customA 100-mL round-bottomed flask equipped with a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 10 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (2×15 mL)
  8. concentrationThe combined filtrate was concentrated under reduced pressure
  9. customThe residue was purified by silica-gel column chromatography
  10. washeluting with dichloromethane/methanol (80:1 to 30:1)

出典と根拠

ORDレコード
ord-f4ca1436db144555b14bfb8ec010a562
出典データセット
uspto-grants-2016_01
特許番号
US09238655B2

反応ノート

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