Water → 2-(2,4-Dimethoxyphenylamino)-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)nicotinamide

HRID 626364Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 626364
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:23]=[CH:22][CH:21]=[CH:20][C:13]=1[C:14]([NH:16][CH2:17][C:18]#[CH:19])=[O:15].[N:24]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:29]=1)=[N+:25]=[N-:26].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>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[NH:11][C:12]1[N:23]=[CH:22][CH:21]=[CH:20][C:13]=1[C:14]([NH:16][CH2:17][C:18]1[N:26]=[N:25][N:24]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:29]=2)[CH:19]=1)=[O:15]

Komponenten

7

Edukt 4

HCID 962WaterHCID 23667548Sodium AscorbateHCID 581200811-(Azidomethyl)-3-phenoxybenzeneHCID 1181260462-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide

Produkt 1

HCID 906810032-(2,4-Dimethoxyphenylamino)-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)nicotinamideAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24462Copper SulfateKatalysatorHCID 6386tert-ButanolLösungsmittel

Versuchsvorschrift

Compound 8 (194 mg, 1 mmol) and 2,4-dimethoxyaniline (9 g, 153 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-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide 10g as pure product. To a solution of 2-(2,4-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide (10 g, 150 mg, 0.48 mmol) and 1-(azidomethyl)-3-phenoxybenzene (12a, 119 mg, 0.53 mmol) in 2:1 mixture of water and tert-butyl alcohol, sodium ascorbate (0.06 mmol) and copper (II) sulphate (0.004 mmol) were added sequentially. The reaction was stirred at room temperature for 10 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 1g (201 mg, 78%); mp: 127-129° C.; 1H NMR (300 MHz, CDCl3) δ 10.30 (s, 1H), 8.25-8.21 (m, 2H), 7.73 (d, J=7.5 Hz 1H), 7.56 (s, 1H), 7.35-7.28 (m, 3H), 7.11 (t, J=7.5 Hz, 1H), 6.99-6.90 (m, 5H), 6.59-6.47 (m, 3H), 5.45 (s, 2H), 4.67 (d, J=5.2 Hz, 2H), 3.87 (s, 6H), 3.79 ppm (s, 3H); MS (ESI m/z): 537 [M+H]+. Yield: 78%

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-bc2d4797522940d4ba97e6d14b5c430b
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309225B2

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