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2,6-Diiodopyrazine → 2-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro benzylamide

HRID 1879155
ノート
印刷プレビュー

反応式

HRID 1879155 の反応式
[F:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13](Br)=[N:12][C:11]=2[CH3:16])=[O:9])=[CH:4][CH:3]=1.[I:19][C:20]1[CH:25]=[N:24][CH:23]=[C:22](I)[N:21]=1>O1CCCC1.CN(C)C=O.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:18]=[CH:17][C:5]([CH2:6][NH:7][C:8]([C:10]2[S:14][C:13]([C:22]3[CH:23]=[N:24][CH:25]=[C:20]([I:19])[N:21]=3)=[N:12][C:11]=2[CH3:16])=[O:9])=[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 110020782,6-DiiodopyrazineHCID 666314052-Bromo-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

生成物 1

HCID 866455582-(6-Iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro benzylamide収率 10.5%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide
溶媒
HCID 8028Tetrahydrofuran溶媒

反応条件

温度
100 °C

実験手順

Part B. An oven-dried sealed tube was charged with 2-bromo-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (1.0 g, 3.03 mmol, 1.0 equiv). The sealed tube was purged with nitrogen and Rieke zinc (10 mL, 10 g of zinc in 100 mL of tetrahydrofuran) was added. The reaction was heated in the microwave oven for 15 min at 100° C. Stirring was stopped and the remaining zinc was allowed to settle. The supernatant containing the zinc reagent was transferred via syringe to a solution of 2,6-diiodopyrazine (704 mg, 2.1 mmol, 0.7 equiv), Pd(PPh3)4 (175 mg, 0.2 mmol, 5 mol %) in tetrahydrofuran (2 mL) and dimethyl formamide (0.1 mL). The reaction mixture was purged with nitrogen for 10 min, then stirred at 140° C. for 20 hr. After cooling, the solvent was removed in vacuo and the crude product was purified by column chromatography [SiO2, ethyl acetate/heptane, 10:90 to 40:60, v/v] to afford 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide (100 mg, 7%). MS (M+H)+=455.1, Rt=1.53 min.

後処理

  1. customAn oven-dried sealed tube
  2. customThe sealed tube was purged with nitrogen and Rieke zinc (10 mL, 10 g of zinc in 100 mL of tetrahydrofuran)
  3. additionwas added
  4. additionThe supernatant containing the zinc reagent
  5. customThe reaction mixture was purged with nitrogen for 10 min
  6. stirringstirred at 140° C. for 20 hr
  7. temperatureAfter cooling
  8. customthe solvent was removed in vacuo
  9. customthe crude product was purified by column chromatography [SiO2, ethyl acetate/heptane, 10:90 to 40:60

出典と根拠

ORDレコード
ord-454485d9a7f54213a5af67761fb45243
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08314138B2

反応ノート

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