5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indole → tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate

HRID 1529418ノート

反応式

HRID 1529418 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]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2I.[CH3:29][O:30][C:31]1[CH:36]=[C:35]([Sn](C)(C)C)[N:34]=[C:33]([N:41]2[CH2:46][CH2:45][CH:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:43][CH2:42]2)[N:32]=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>[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]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2[C:35]1[CH:36]=[C:31]([O:30][CH3:29])[N:32]=[C:33]([N:41]2[CH2:46][CH2:45][CH:44]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:52])([CH3:51])[CH3:53])[CH2:43][CH2:42]2)[N:34]=1

参加物

6

反応物 2

HCID 679602665-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indoleHCID 86709790Tert-butyl (1-(4-methoxy-6-(trimethylstannyl)pyrimidin-2-yl)piperidin-4-yl)carbamate

生成物 1

HCID 86709789tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate収率 43.5%

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
90 °C

実験手順

To a solution of 5-(2,6-difluorophenyl)-3-iodo-1-tosyl-1H-indole (0.107 g, 0.2 mmol) and tert-butyl (1-(4-methoxy-6-(trimethylstannyl)pyrimidin-2-yl)piperidin-4-yl)carbamate (0.1 g, 0.2 mmol) in DMF (2 mL) was added Pd(PPh3)4 (23 mg, 0.02 mmol) and CuI (42 mg, 0.22 mmol) and argon gas was bubbled for 15 min. The reaction was heated at 90° C. for 1 h then quenched with water. The suspension was extracted with EtOAc and the organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified with basic alumina chromatography (eluting with 50% EtOAc in petroleum ether) to give tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate (60 mg, 41%). MS (ESI, pos. ion) m/z: 690.2 (M+1); 1H-NMR (DMSO-d6, 300 MHz): δ ppm 8.71 (s, 1H), 8.61 (s, 1H), 8.10-8.20 (m, 3H), 7.42-7.52 (m, 4H), 7.20-7.25 (m, 3H), 6.76 (m, 1H), 4.56 (d, J=12.9 Hz, 2H), 3.87 (s, 3H), 3.32 (d, J=9 Hz, 3H), 3.03 (m, 2H) 2.33 (s, 3H), 1.74 (d, J=12.9 Hz, 2H), 1.3 (s, 9H).

後処理

  1. customwas bubbled for 15 min
  2. customthen quenched with water
  3. extractionThe suspension was extracted with EtOAc
  4. dry with materialthe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with basic alumina chromatography (eluting with 50% EtOAc in petroleum ether)

出典と根拠

ORDレコード
ord-9ab187c6562a42b4a705f2afaec88881
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…