Cesium carbonate → 5-Bromo-1-methyl-3-(6-(trifluoromethyl)pyridazin-3-ylamino)pyridin-2(1H)-one

HRID 1022169ノート

反応式

HRID 1022169 の反応式
[F:1][C:2]([F:11])([F:10])[C:3]1[N:8]=[N:7][C:6]([NH2:9])=[CH:5][CH:4]=1.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.Br[C:55]1[C:56](=[O:63])[N:57]([CH3:62])[CH:58]=[C:59]([Br:61])[CH:60]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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:61][C:59]1[CH:60]=[C:55]([NH:9][C:6]2[N:7]=[N:8][C:3]([C:2]([F:1])([F:10])[F:11])=[CH:4][CH:5]=2)[C:56](=[O:63])[N:57]([CH3:62])[CH:58]=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 598058596-(Trifluoromethyl)pyridazin-3-amine

生成物 1

HCID 866845485-Bromo-1-methyl-3-(6-(trifluoromethyl)pyridazin-3-ylamino)pyridin-2(1H)-one収率 89%

試薬・触媒・溶媒 2

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

反応条件

温度
90 °C

実験手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 301a (750 mg, 4.6 mmol), XantPhos (532 mg, 0.92 mmol), Pd2dba3 (421 mg, 0.46 mmol), 2-bromo-4-chloronicotinaldehyde (H-001) (1.84 g, 6.9 mmol), Cs2CO3 (3.0 g, 9.2 mmol), and 1,4-dioxane (50 mL). The system was subjected to three cycles of vacuum/argon flush and heated at 90° C. for overnight. After the completion of the reaction, the mixture was filtered and the solid was washed with methanol (30 mL). The combined filtrate was evaporated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 20:1 dichloromethane/methanol to afford 301b (1.38 g, 89%) as a yellow solid. MS-ESI: [M+H]+ 350.8

後処理

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customflush
  3. customAfter the completion of the reaction
  4. filtrationthe mixture was filtered
  5. washthe solid was washed with methanol (30 mL)
  6. customThe combined filtrate was evaporated under reduced pressure
  7. customthe residue was purified by silica-gel column chromatography
  8. washeluting with 20:1 dichloromethane/methanol

出典と根拠

ORDレコード
ord-65cbc9a16f6148b5afe0005b6dcf191d
出典データセット
uspto-grants-2014_05
特許番号
US08716274B2

反応ノート

読み込み中…