Nitrogen → tert-butyl 1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-3-ylcarbamate

HRID 1529281ノート

反応式

HRID 1529281 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2I.C([Sn](CCCC)(CCCC)[C:30]1[N:35]=[C:34]([N:36]2[CH2:41][CH2:40][CH2:39][CH:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:37]2)[CH:33]=[N:32][CH:31]=1)CCC.N#N.O>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][O:19]1)[N:13]=[C:12]2[C:30]1[N:35]=[C:34]([N:36]2[CH2:41][CH2:40][CH2:39][CH:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:37]2)[CH:33]=[N:32][CH:31]=1

参加物

8

反応物 4

HCID 947NitrogenHCID 962WaterHCID 67958112Tert-butyl 1-(6-(tributylstannyl)pyrazin-2-yl)piperidin-3-ylcarbamateHCID 679597535-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole

生成物 1

HCID 67959937tert-butyl 1-(6-(5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yl)piperidin-3-ylcarbamate収率 66%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

A solution of 5-(2,6-difluorophenyl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (400 mg, 0.91 mmol) and tert-butyl 1-(6-(tributylstannyl)pyrazin-2-yl)piperidin-3-ylcarbamate (520 mg, 0.91 mmol) in DMF (9.1 mL) was purged with N2 for 15 min and added CuI (225 mg, 1.18 mmol) and Pd(PPh3)4 (105 mg, 0.09 mmol). The reaction mixture was heated at 80° C. for 2 h and cooled to RT. To the reaction mixture was added water and precipitate was formed. The precipitate was collected by filtration, washed with water and dried overnight to give crude product. The crude was purified by chromatography (eluting with 0-10% MeOH and DCM) to obtain the title compound (350 mg, 66% yield). MS (ESI, pos. ion) m/z: 591 (M+1).

後処理

  1. temperaturecooled to RT
  2. customprecipitate was formed
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water
  5. customdried overnight
  6. customto give crude product
  7. customThe crude was purified by chromatography (eluting with 0-10% MeOH and DCM)

出典と根拠

ORDレコード
ord-7f699f1eed884c6a8d58624d4d4c1fb4
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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