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6-fluoro-1-methyl-3-(tributylstannyl)-1H-indazole → methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate

HRID 246569
ノート
印刷プレビュー

反応式

HRID 246569 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Sn](CCCC)(CCCC)CCCC)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.Br[C:26]1[N:27]=[C:28]2[C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][N:32]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:45])([CH3:44])[CH3:43])[C:29]2=[N:30][CH:31]=1>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:10]=[C:9]2[C:5]([C:6]([C:26]3[N:27]=[C:28]4[C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][N:32]([CH2:39][O:40][C:41](=[O:46])[C:42]([CH3:44])([CH3:43])[CH3:45])[C:29]4=[N:30][CH:31]=3)=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 2

HCID 712803076-fluoro-1-methyl-3-(tributylstannyl)-1H-indazoleHCID 86677991methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate

生成物 1

HCID 71280132methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate収率 85.2%

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 stirred solution of 6-fluoro-1-methyl-3-(tributylstannyl)-1H-indazole (0.51 g, 0.616 mmol), methyl 2-bromo-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate (0.18 g, 0.486 mmol) in 6 mL of DMF were added CuI (0.04 g, 0.21 mmol) and Pd(PPh3)4 (0.057 g, 0.045 mmol) in one portion under nitrogen at room temperature. Then the reaction mixture was degassed by bubbling nitrogen for 10 minutes and stirred at 90° C. under nitrogen for 16 hours. The solvent was evaporated at 70° C. under reduced pressure and the residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with a mixture of ethyl acetate and petroleum ether (1:1, v/v) to give methyl 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylate (0.182 g, 85.2%) as a yellow solid. LCMS: (M+H)+=440; 1H NMR (300 MHz, DMSO): δ 9.13 (s, 1H), 8.83-8.78 (m, 1H), 8.70 (s, 1H), 7.63 (dd, 1H, J1=9.6 Hz, J2=2.1 Hz), 7.23 (dt, 1H, J1=9.3 Hz, J2=2.1 Hz), 6.30 (s, 2H), 4.13 (s, 3H), 3.92 (s, 3H), 1.08 (s, 9H).

後処理

  1. customThen the reaction mixture was degassed
  2. customby bubbling nitrogen for 10 minutes
  3. customThe solvent was evaporated at 70° C. under reduced pressure
  4. customthe residue was purified by column chromatography (silica gel, 200-300 mesh
  5. washeluting with a mixture of ethyl acetate and petroleum ether (1:1

出典と根拠

ORDレコード
ord-ad76c405be7d4c6bb43327b3201c117b
出典データセット
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08658646B2

反応ノート

読み込み中…

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