Nitrogen → 3-(2-chloropyrimidin-4-yl)-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529289ノート

反応式

HRID 1529289 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.[Cl:25][C:26]1[N:31]=[C:30]([Sn](CCCC)(CCCC)CCCC)[CH:29]=[CH:28][N:27]=1.N#N>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>[Cl:25][C:26]1[N:31]=[C:30]([C:12]2[C:11]3[C:15](=[CH:16][CH:17]=[C:9]([C:3]4[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=4[F:8])[CH:10]=3)[N:14]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[N:13]=2)[CH:29]=[CH:28][N:27]=1

参加物

7

反応物 3

HCID 947NitrogenHCID 468399532-Chloro-4-(tributylstannyl)pyrimidineHCID 679597535-(2,6-difluoro-phenyl)-3-iodo-1-(tetrahydro-pyran-2-yl)-1H-indazole

生成物 1

HCID 867097653-(2-chloropyrimidin-4-yl)-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole収率 52.1%

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
90 °C

実験手順

To a solution of 5-(2,6-difluorophenyl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole 14 (0.2 g, 0.45 mmol) and 2-Chloro-4-tributylstannanyl-pyrimidine 20a (0.27 g, 0.68 mmol) in DMF was bubbled N2 for 15 min and added CuI (0.052 g, 0.54 mmol) and Pd(PPh3)4 (0.1 g, 0.025 mmol). The reaction mixture was heated at 90° C. for 2 h and cooled to RT. The reaction mixture was quenched with water and precipitate was formed. The resulting precipitate was collected by filtration, washed with water, and dried to yield crude product. Purification by silica gel column chromatography, eluting with 5-10% EtOAc and hexanes to obtain the title compound (0.1 g, 38%). MS (ESI, pos. ion) m/z: 427.0 (M+1).

後処理

  1. temperaturecooled to RT
  2. customThe reaction mixture was quenched with water
  3. customprecipitate was formed
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water
  6. customdried
  7. customto yield crude product
  8. customPurification by silica gel column chromatography
  9. washeluting with 5-10% EtOAc and hexanes

出典と根拠

ORDレコード
ord-752b81ea888846b2bdf1d20be594d5a4
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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