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

HRID 407733ノート

反応式

HRID 407733 の反応式
[F:1][CH:2]([F:14])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]2[N:10]=[C:11]([NH2:13])[CH:12]=[C:6]2[CH2:5]1.Br[C:16]1[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[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:13][C:11]2[CH:12]=[C:6]3[CH2:5][N:4]([CH2:3][CH:2]([F:1])[F:14])[CH2:9][CH2:8][N:7]3[N:10]=2)[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=1

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 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 866840035-(2,2-Difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

生成物 1

HCID 866840045-Bromo-3-(5-(2,2-difluoroethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)-1-methylpyridin-2(1H)-one収率 72.1%

試薬・触媒・溶媒 2

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

実験手順

A 50-mL round-bottomed flask equipped with a reflux condenser was charged with 135b (290 mg, 1.43 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (383 mg, 1.43 mmol), cesium carbonate (932 mg, 2.86 mmol), and 1,4-dioxane (20 mL). After bubbling nitrogen through the suspension for 10 minutes, xantphos (82 mg, 0.143 mmol) and Pd2(dba)3 (65 mg, 0.072 mmol) were added. The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (30 mL). The combined organic 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 135c (400 mg, 72%) as a yellow solid. MS-ESI: [M+H]+ 387.8

後処理

  1. customA 50-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 (30 mL)
  8. concentrationThe combined organic 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-1d0b798096a349948f79733dbd410859
出典データセット
uspto-grants-2014_06
特許番号
US08754077B2

反応ノート

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