Cesium carbonate → (5-Bromo-pyridin-2-yl)-(2-methyl-6-trifluoromethyl-pyridin-3-yl)-amine

HRID 1404237ノート

反応式

HRID 1404237 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH3:9][C:10]1[C:15]([NH2:16])=[CH:14][CH:13]=[C:12]([C:17]([F:20])([F:19])[F:18])[N:11]=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.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([NH:16][C:15]2[C:10]([CH3:9])=[N:11][C:12]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:14]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 693532,5-DibromopyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 35218502-methyl-6-(trifluoromethyl)pyridin-3-amine

生成物 1

HCID 66615910(5-Bromo-pyridin-2-yl)-(2-methyl-6-trifluoromethyl-pyridin-3-yl)-amine

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
100 °C

実験手順

2,5-dibromopyridine (474 mg, 2 mmol) and 2-Methyl-6-trifluoromethyl-pyridin-3-ylamine (352 g, 2 mmol) were dissolved in 1,4-dioxane (4 mL) in a pressure vessel. Pd2dba3 (55 mg, 0.06 mmol) and XANTPHOS (46 mg, 0.08 mmol) were added, followed by cesium carbonate (1.3 g, 4 mmol). The mixture was sparged with nitrogen for 10 minutes, then the vessel was sealed and heated at 100° C. for 18 hours. The mixture was partitioned between EtOAc and saturated aqueous NH4Cl, then the organic layer was washed with brine, dried with magnesium sulfate, filtered, and concentrated via rotary evaporation. The crude material was purified via column chromatography on silica gel, eluting with a gradient of EtOAc/hexanes (7-60%) to obtain the target compound as a solid: 1H NMR (400 MHz, CDCl3) δ ppm 2.62 (s, 3 H) 6.36 (br. s., 1 H) 6.75 (d, J=8.59 Hz, 1 H) 7.53 (d, J=8.34 Hz, 1 H) 7.69 (dd, J=8.84, 2.53 Hz, 1 H) 8.32-8.37 (m, 2 H); MS (M+H)+ 334.7.

後処理

  1. customThe mixture was sparged with nitrogen for 10 minutes
  2. customthe vessel was sealed
  3. customThe mixture was partitioned between EtOAc and saturated aqueous NH4Cl
  4. washthe organic layer was washed with brine
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated via rotary evaporation
  8. customThe crude material was purified via column chromatography on silica gel
  9. washeluting with a gradient of EtOAc/hexanes (7-60%)

出典と根拠

ORDレコード
ord-e9ae5b8bf6e44188a4af4efb2123930e
出典データセット
uspto-grants-2014_12
特許番号
US08912208B2

反応ノート

読み込み中…