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

HRID 593094ノート

反応式

HRID 593094 の反応式
[CH3:1][O:2][CH2:3][CH:4]([N:6]1[CH2:11][CH2:10][N:9]2[N:12]=[C:13]([NH2:15])[CH:14]=[C:8]2[CH2:7]1)[CH3:5].Br[C:17]1[C:18](=[O:25])[N:19]([CH3:24])[CH:20]=[C:21]([Br:23])[CH:22]=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:23][C:21]1[CH:22]=[C:17]([NH:15][C:13]2[CH:14]=[C:8]3[CH2:7][N:6]([CH:4]([CH3:5])[CH2:3][O:2][CH3:1])[CH2:11][CH2:10][N:9]3[N:12]=2)[C:18](=[O:25])[N:19]([CH3:24])[CH:20]=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 866845455-(1-Methoxypropan-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-amine

生成物 1

HCID 866845465-Bromo-3-(5-(1-methoxypropan-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrazin-2-ylamino)-1-methylpyridin-2(1H)-one収率 58%

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 single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (40 mL), 300b (400 mg, 1.9 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (H-001) (508 mg, 1.9 mmol), and cesium carbonate (1.24 g, 3.8 mmol). After bubbling nitrogen through the suspension for 20 minutes, xantphos (109 mg, 0.19 mmol) and Pd2(dba)3 (87 mg, 0.095 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 (2×30 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 300c (436 mg, 58%) as yellow solid. MS-ESI: [M+H]+ 396.0

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter bubbling nitrogen through the suspension for 20 minutes
  3. customflush
  4. temperatureheated
  5. temperatureat reflux for 5 h
  6. filtrationfiltered
  7. washThe solid was washed with dichloromethane (2×30 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-a01f70bf3689425e857d779ddc6cedea
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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