Propyne → 6-Methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)-1H-indole

HRID 218860ノート

反応式

HRID 218860 の反応式
I[C:2]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:3]=1[NH:4][C:5](=O)[C:6](F)(F)F.C(N(CC)C(C)C)(C)C.[CH:26]#CC.[CH3:29][O:30][C:31]1[CH:32]=[C:33](I)[CH:34]=[C:35]([O:39][CH3:40])[C:36]=1[O:37][CH3:38].[C:42]([O-:45])([O-])=O.[K+].[K+]>CN(C=O)C.[Cu]I>[CH3:16][O:15][C:12]1[CH:11]=[C:3]2[C:2]([C:6]([C:42](=[O:45])[C:33]3[CH:32]=[C:31]([O:30][CH3:29])[C:36]([O:37][CH3:38])=[C:35]([O:39][CH3:40])[CH:34]=3)=[C:5]([CH3:26])[NH:4]2)=[CH:14][CH:13]=1

参加物

8

反応物 5

HCID 6335Propyne2 回HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2981335-Iodo-1,2,3-trimethoxybenzeneHCID 221434932,2,2-Trifluoro-N-(2-iodo-5-methoxy-phenyl)-acetamide

生成物 1

HCID 104733846-Methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)-1H-indole収率 55.3%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 2-iodo-5-methoxy-N-trifloroacetylaniline (Flynn et al, J. Med. Chem., 2002, 45(12), 2670; 0.508 g; 1.5 mmol), Cl2Pd(PPh3)2 (0.102 g; 0.145 mmol); CuI (0.016 g; 0.085 mmol), anhydrous N,N-diisopropyl ethylamine (1 ml) in anhydrous DMF (10 ml) was cooled to −40° C., degassed under reduced pressure and saturated with dry N2. The propyne gas (0.53 g; 13.3 mmol) was added to it at −40° C. The reaction flask was sealed with septum and allowed to warm up to room temperature and stirred for 3 h. After removal of excess of propyne under reduced pressure 3,4,5-trimethoxyphenyl iodide (0.5 g; 1.7 mmol) was added to it, followed by dry K2CO3 (0.621 g; 4.5 mmol). The resulting mixture was degassed in vacuo and saturated with CO gas and stirred for 3 h under CO balloon pressure. The mixture was diluted to 50 ml with diethyl ether, washed with H2O (2×15 ml), brine (10 ml), dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness under reduced pressure. The residue was purified by flash column chromatography (SiO2; CH2Cl2) to give pure title compound (0.295 g; 55%) as a yellow crystals:

後処理

  1. customdegassed under reduced pressure and saturated with dry N2
  2. customThe reaction flask was sealed with septum
  3. additionwas added to it
  4. customThe resulting mixture was degassed in vacuo and saturated with CO gas
  5. stirringstirred for 3 h under CO balloon pressure
  6. additionThe mixture was diluted to 50 ml with diethyl ether
  7. washwashed with H2O (2×15 ml), brine (10 ml)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. customfiltrate evaporated to dryness under reduced pressure
  11. customThe residue was purified by flash column chromatography (SiO2; CH2Cl2)

出典と根拠

ORDレコード
ord-0b67c7c758bd4467bb8c06f883c1e5d3
出典データセット
uspto-grants-2012_06
特許番号
US08198466B2

反応ノート

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