2-Chloro-6-(tributylstannyl)pyrazine → 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1529375ノート

反応式

HRID 1529375 の反応式
[CH:1]1([C:4]2[N:9]=[C:8]([C:10]3[CH:11]=[C:12]4[C:16](=[CH:17][CH:18]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=[C:13]4I)[CH:7]=[N:6][CH:5]=2)[CH2:3][CH2:2]1.[Cl:26][C:27]1[CH:32]=[N:31][CH:30]=[C:29]([Sn](CCCC)(CCCC)CCCC)[N:28]=1>CN(C=O)C.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.[Cu]I>[Cl:26][C:27]1[N:28]=[C:29]([C:13]2[C:12]3[C:16](=[CH:17][CH:18]=[C:10]([C:8]4[CH:7]=[N:6][CH:5]=[C:4]([CH:1]5[CH2:3][CH2:2]5)[N:9]=4)[CH:11]=3)[N:15]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][O:20]3)[N:14]=2)[CH:30]=[N:31][CH:32]=1

参加物

6

反応物 2

HCID 117740572-Chloro-6-(tributylstannyl)pyrazineHCID 679600395-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

生成物 1

HCID 867097793-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole収率 35.5%

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
105 °C

実験手順

A glass microwave reaction vessel was charged with 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol), 2-chloro-6-(tributylstannyl)pyrazine (190 mg, 0.47 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol) and CuI (6 mg, 0.031 mmol) in DMF (1 mL). Argon was bubbled through the mixture for 5 min. The tube was sealed and the mixture was heated to 105° C. for 2 h. The reaction was diluted with EtOAc and water and filtered through celite. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide 3-(6-chloropyrazin-2-yl)-5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (48 mg, 0.11 mmol, 35% yield) as a light-yellow solid. MS (ESI, pos. ion) m/z: 433.0 (M+1).

後処理

  1. customA glass microwave reaction vessel
  2. customArgon was bubbled through the mixture for 5 min
  3. customThe tube was sealed
  4. additionThe reaction was diluted with EtOAc and water
  5. filtrationfiltered through celite
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with a gradient of 0-50% EtOAc in hexanes

出典と根拠

ORDレコード
ord-7be510b86e5248bd92a2b5832f49840a
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

読み込み中…