Trimethylsilylacetylene → N-(2-chlorophenyl)-8-ethynyl-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

HRID 1949703ノート

反応式

HRID 1949703 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([N:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[Cl:25])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:26]=1.C[Si]([C:31]#[CH:32])(C)C>C(N(CC)CC)C.O.[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:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[N:17]([CH3:18])[C:15]([C:13]1[S:12][C:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:31]#[CH:32])=[CH:26][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]

参加物

7

反応物 2

HCID 66111TrimethylsilylacetyleneHCID 442424278-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

生成物 1

HCID 44242300N-(2-chlorophenyl)-8-ethynyl-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8471Triethylamine溶媒

反応条件

温度
130 °C

実験手順

A solution of 8-bromo-N-(2-chlorophenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide 150 (50 mg, 0.11 mmol) in triethylamine (2 mL) containing CuI (2.1 mg, 0.011 mmol) was degassed with bubbling nitrogen for 10 min. Pd(PPh3)4 (13 mg, 0.011 mmol) was added followed by trimethylsilylacetylene (5 equiv). The reaction vessel was sealed and heated in the microwave at 130° C. for 30 min. The cooled mixture was diluted with water and extracted with ethylacetate. The combined organics were concentrated and the residue dissolved in 2 mL methanol. The solution was treated with potassium carbonate (100 mg) and the suspension stirred for 2 hr at room temperature. The reaction mixture was concentrated, diluted with water and extracted with ethylacetate. The combined organics were concentrated and the residue purified by reverse phase HPLC to give 133. MS: (ESI+) 394.1.

後処理

  1. customwas degassed with bubbling nitrogen for 10 min
  2. customThe reaction vessel was sealed
  3. extractionextracted with ethylacetate
  4. concentrationThe combined organics were concentrated
  5. dissolutionthe residue dissolved in 2 mL methanol
  6. additionThe solution was treated with potassium carbonate (100 mg)
  7. concentrationThe reaction mixture was concentrated
  8. additiondiluted with water
  9. extractionextracted with ethylacetate
  10. concentrationThe combined organics were concentrated
  11. customthe residue purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-7d21a23877c74fbe99ed6011f9d338e3
出典データセット
uspto-grants-2013_03
特許番号
US08399690B2

反応ノート

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