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 528719노트

반응식

HRID 528719 반응식
[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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 312751,4-Dioxane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-10edd761eee8495cb52ba8f5a814973c
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346816B2

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