Cesium carbonate → tert-butyl N-[(3S)-1-[3-fluoro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

HRID 57915ノート

反応式

HRID 57915 の反応式
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[CH:14]=[N:15][NH:16][C:10]=3[CH:9]=2)[CH:5]=[N:4][CH:3]=1.Cl[C:18]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]2)[C:21]([F:38])=[CH:20][CH:19]=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>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:38][C:21]1[C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:25]2)=[N:23][C:18]([N:16]2[C:10]3[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([CH3:1])[N:7]=4)[N:13]=[CH:12][C:11]=3[CH:14]=[N:15]2)=[CH:19][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 867070806-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridineHCID 86707106tert-butyl N-[(3S)-1-(6-chloro-3-fluoro-2-pyridyl)-3-piperidyl]carbamate

生成物 1

HCID 86707107tert-butyl N-[(3S)-1-[3-fluoro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate収率 26.9%

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
110 °C

実験手順

A mixture of 6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine (0.83325 mmol; 176 mg), tert-butyl N-[(3S)-1-(6-chloro-3-fluoro-2-pyridyl)-3-piperidyl]carbamate (0.8378 mmol; 276.3 mg), cesium carbonate (1.6665 mmol; 543.00 mg), Xantphos (0.14165 mmol; 84.500 mg), and tris(dibenzylideneacetone)dipalladium(0) (0.083325 mmol; 77.074 mg) in 1,4-Dioxane (10 mL) was purged with Argon, then sealed and stirred at 110° C. overnight. The mixture was cooled to room temperature and filtered through Celite. The filtrate was concentrated and the residue was purified on silica eluted with 0 to 100% EtOAc in Heptane to afford tert-butyl N-[(3S)-1-[3-fluoro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (113.1 mg, 16%).

後処理

  1. customwas purged with Argon
  2. customsealed
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified on silica
  7. washeluted with 0 to 100% EtOAc in Heptane

出典と根拠

ORDレコード
ord-8608efd8f98e424a935b2aac20123f75
出典データセット
uspto-grants-2016_09
特許番号
US09434725B2

反応ノート

読み込み中…