Water → N-((1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(4-methoxyphenylamino) nicotinamide

HRID 626387ノート

反応式

HRID 626387 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:21]=[CH:20][CH:19]=[CH:18][C:11]=2[C:12]([NH:14][CH2:15][C:16]#[CH:17])=[O:13])=[CH:5][CH:4]=1.[N:22]([CH2:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[CH:27]=1)=[N+:23]=[N-:24].O.O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>S([O-])([O-])(=O)=O.[Cu+2].C(O)(C)(C)C>[CH3:33][O:32][C:30]1[CH:31]=[C:26]([CH:27]=[C:28]([O:34][CH3:35])[CH:29]=1)[CH2:25][N:22]1[CH:17]=[C:16]([CH2:15][NH:14][C:12](=[O:13])[C:11]2[CH:18]=[CH:19][CH:20]=[N:21][C:10]=2[NH:9][C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:24]=[N:23]1

参加物

7

反応物 4

HCID 962WaterHCID 115212321-(Azidomethyl)-3,5-dimethoxybenzeneHCID 23667548Sodium AscorbateHCID 1181259512-(4-methoxyphenylamino)-N-(prop-2-ynyl)nicotinamide

生成物 1

HCID 90681012N-((1-(3,5-Dimethoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(4-methoxyphenylamino) nicotinamide収率 78.3%

試薬・触媒・溶媒 2

HCID 24462Copper Sulfate触媒HCID 6386tert-Butanol溶媒

実験手順

Compound 8 (194 mg, 1 mmol) and 4-methoxyaniline (9e, 123 mg, 1 mmol) were taken in ethylene glycol and heated at 140° C. for 6 h. Then the reaction mixture was cooled and extracted with ethyl acetate from the aqueous layer and concentrated in vacuum. The compound was further purified by column chromatography using 60-120 silica gel to obtain 2-(4-methoxyphenylamino)-N-(prop-2-ynyl)nicotinamide 10e as pure product. To a solution of 2-(4-methoxyphenylamino)-N-(prop-2-ynyl)nicotinamide (10e, 150 mg, 0.53 mmol) and 1-(azidomethyl)-3,5-dimethoxybenzene (12d, 102 mg, 0.58 mmol) in 2:1 mixture of water and tert-butyl alcohol, sodium ascorbate (0.06 mmol) and copper (II) sulphate (0.005 mmol) were added sequentially. The reaction was stirred at room temperature for 11 h, TLC analysis indicated completion of reaction. The reaction mixture was concentrated under vacuum and extracted with EtOAc to give crude product. The crude was purified by column chromatography to afford pure product 6e (197 mg, 78%); mp: 147-149° C.; 1H NMR (300 MHz, CDCl3) δ 10.17 (s, 1H), 8.24 (dd, J=4.9, 1.7 Hz, 1H), 7.55-7.48 (dd, J=7.7, 1.7 Hz, 1H), 7.17 (t, J=5.0 Hz, 1H), 6.87 (d, J=8.8 Hz, 2H), 6.62-6.57 (m, 1H), 6.42-6.39 (m, 3H), 5.42 (s, 2H), 4.66 (d, J=5.4 Hz, 2H), 3.79 (s, 3H), 3.75 ppm (s, 6H) MS (ESI m/z): 475 [M+H]+. Yield: 78%

後処理

  1. additionwere added sequentially
  2. customcompletion of reaction
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. extractionextracted with EtOAc
  5. customto give crude product
  6. customThe crude was purified by column chromatography

出典と根拠

ORDレコード
ord-4bacb4d3809a4735986eabbe8bdb701e
出典データセット
uspto-grants-2016_04
特許番号
US09309225B2

反応ノート

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