1,4-Dioxane → N-(4-(4-(4-chlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)pyridin-2-yl)acetamide

HRID 1615502ノート

反応式

HRID 1615502 の反応式
Br[C:2]1[S:6][C:5]2[C:7](=[O:17])[CH2:8][CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.C[Sn](C)(C)[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=1.O1CCOCC1.[Cl-].[Li+]>[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:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[C:4]3[CH:3]=[C:2]([C:20]4[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=4)[S:6][C:5]=3[C:7](=[O:17])[CH2:8]2)=[CH:11][CH:12]=1

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 433294Lithium ChlorideHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 681829442-bromo-4-(4-chlorophenyl)-4H-cyclopenta[b]thiophen-6(5H)-one

生成物 1

HCID 56971355N-(4-(4-(4-chlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)pyridin-2-yl)acetamide収率 81.5%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒

反応条件

温度
90 °C

実験手順

To a 20 mL vial was added a solution of 2-bromo-4-(4-chlorophenyl)-4,5-dihydro-6H-cyclopenta[b]thiophen-6-one (0.046 g, 0.141 mmol) and N-[4-(trimethylstannyl)pyridin-2-yl]acetamide (0.063 g, 0.211 mmol) in anhydrous 1,4-dioxane (2.00 mL, 25.63 mmol) was degassed for 10 minutes. Lithium chloride (0.018 g, 0.42 mmol) and copper(I) iodide (0.008 g, 0.043 mmol) was added followed by tetrakis(triphenylphosphine)palladium(0) (0.008 g, 0.007 mmol). The reaction mixture was heated to 90° C. and allowed to stir for 18 h. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (2.00 mL) and extracted with EtOAc (2.00 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was dry loaded onto silica gel and then purified using an ISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min) to afford the title compound (0.044 g, 78%) as a yellow oil. LC/MS (AA) ES+ 383, 385. 1H NMR (dmso-d6, 400 MHz): δ 10.68 (s, 1H), 8.40 (s, 1H), 8.36 (d, 1H), 7.66 (s, 1H), 7.50 (dd, 1H), 7.42-7.40 (m, 2H), 7.30-7.28 (m, 2H), 4.72 (dd, 1H), 3.48 (dd, 1H), 2.82 (dd, 1H), 2.11 (s, 3H).

後処理

  1. customwas degassed for 10 minutes
  2. temperatureThe reaction was cooled to ambient temperature
  3. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (2.00 mL)
  4. extractionextracted with EtOAc (2.00 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dry with materialThe crude material was dry
  9. custompurified
  10. customan ISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min)

出典と根拠

ORDレコード
ord-f76955b90113439eb396cc4c7223fcc0
出典データセット
uspto-grants-2014_07
特許番号
US08765746B2

反応ノート

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