Nitrogen → tert-butyl N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]carbamate

HRID 524885ノート

反応式

HRID 524885 の反応式
[CH3:1][C:2]1([CH3:42])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=C[C:3]1=2.[N:43]#N.Br[C:46]1[CH:47]=[N:48][CH:49]=[C:50]([F:67])[C:51]=1[N:52]1[CH2:57][CH2:56][CH:55]([C:58]([N:60]2[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]2)=[O:59])[CH2:54][CH2:53]1.[C:68]([O-:71])([O-])=[O:69].[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]>[F:67][C:50]1[C:51]([N:52]2[CH2:57][CH2:56][CH:55]([C:58]([N:60]3[CH2:65][CH2:64][N:63]([CH3:66])[CH2:62][CH2:61]3)=[O:59])[CH2:54][CH2:53]2)=[C:46]([NH:43][C:68](=[O:69])[O:71][C:2]([CH3:42])([CH3:3])[CH3:1])[CH:47]=[N:48][CH:49]=1

参加物

7

反応物 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86720941(1-(3-Bromo-5-fluoropyridin-4-yl)piperidin-4-yl)(4-methylpiperazin-1-yl)methanone

生成物 1

HCID 86720942tert-butyl N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]carbamate

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

In an alternative method to Step 3, above, Tris(dibenzylideneacetone)dipalladium (1.189 g, 1.298 mmol) and xantphos (1.502 g, 2.596 mmol) were added to a degassed (3×vacuum/N2 cycles) mixture of [1-(3-bromo-5-fluoro-4-pyridyl)-4-piperidyl]-(4-methylpiperazin-1-yl)methanone 19 (10 g, 25.96 mmol) and Cs2CO3 (16.92 g, 51.92 mmol) in dioxane (150 mL) under N2. The mixture was stirred at 100° C. overnight. The reaction was cooled to ambient temperature and the precipitate was filtered off and washed with EtOAc (50 mL). The filtrate was partitioned between EtOAc and water. The combined organic layers were washed with water, brine, dried (MgSO4) and concentrated in vacuo to leave tert-butyl N-[5-fluoro-4-[4-(4-methylpiperazine-1-carbonyl)-1-piperidyl]-3-pyridyl]carbamate as a red solid that was used in next step without further purification. MS (ES+) 422.2.

後処理

  1. customa degassed
  2. temperatureThe reaction was cooled to ambient temperature
  3. filtrationthe precipitate was filtered off
  4. washwashed with EtOAc (50 mL)
  5. customThe filtrate was partitioned between EtOAc and water
  6. washThe combined organic layers were washed with water, brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-41d9d89506894c529df598cfdeab7091
出典データセット
uspto-grants-2016_05
特許番号
US09340546B2

反応ノート

読み込み中…