Triethylamine → 10-Azetidin-1-yl-3-pyridin-2-ylethynyl-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid tert-butyl ester

HRID 528719ノート

反応式

HRID 528719 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:26][CH2:25][C:12]2=[C:13]([N:21]3[CH2:24][CH2:23][CH2:22]3)[N:14]3[C:18]([N:19]=[C:11]2[CH2:10][CH2:9]1)=[C:17](I)[CH:16]=[N:15]3)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)#[CH:28].C(N(CC)CC)C>[Cu]I.O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:26][CH2:25][C:12]2=[C:13]([N:21]3[CH2:24][CH2:23][CH2:22]3)[N:14]3[C:18]([N:19]=[C:11]2[CH2:10][CH2:9]1)=[C:17]([C:28]#[C:27][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1)[CH:16]=[N:15]3)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 3

HCID 8471TriethylamineHCID 137268EthynylpyridineHCID 6797946210-Azetidin-1-yl-3-iodo-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid tert-butyl ester

生成物 1

HCID 6797930110-Azetidin-1-yl-3-pyridin-2-ylethynyl-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

実験手順

To 0.1 g (0.21 mmol) 10-azetidin-1-yl-3-iodo-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid tert-butyl ester in a sealed tube under nitrogen was added 3 mL of dioxane and the mixture was degassed with nitrogen for 3 minutes. 14.7 mg (0.02 mmol) 1,1′-bis-(diphenylphosphino)-ferrocenedichloro palladium (II) was added and the reaction mixture was stirred at room temperature for 30 minutes. 86 μL (0.85 mmol) 2-ethynyl pyridine was added followed by 0.53 mL (3.8 mmol) triethylamine and 4 mg (0.02 mmol) CuI, and the reaction was stirred at 60° C. for 16 hours under nitrogen. The mixture was cooled to room temperature and partitioned between 20 mL EtOAc and 20 mL saturated ammonium chloride. The mixture was extracted with EtOAc (3×10 mL), the organic layers combined, washed with 20 mL brine, and dried with MgSO4. After filtration and evaporation of the solvent the desired product was purified by column chromatography (silica, heptane/EtOAc 9:1 to 3:7).

後処理

  1. customthe mixture was degassed with nitrogen for 3 minutes
  2. stirringthe reaction was stirred at 60° C. for 16 hours under nitrogen
  3. temperatureThe mixture was cooled to room temperature
  4. custompartitioned between 20 mL EtOAc and 20 mL saturated ammonium chloride
  5. extractionThe mixture was extracted with EtOAc (3×10 mL)
  6. washwashed with 20 mL brine
  7. dry with materialdried with MgSO4
  8. filtrationAfter filtration and evaporation of the solvent the desired product
  9. customwas purified by column chromatography (silica, heptane/EtOAc 9:1 to 3:7)

出典と根拠

ORDレコード
ord-10edd761eee8495cb52ba8f5a814973c
出典データセット
uspto-grants-2016_05
特許番号
US09346816B2

反応ノート

読み込み中…