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

HRID 626368
Notes
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Reaction equation

HRID 626368 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[N:23]=[CH:22][CH:21]=[CH:20][C:13]=2[C:14]([NH:16][CH2:17][C:18]#[CH:19])=[O:15])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[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>[CH3:10][O:9][C:7]1[CH:6]=[C:5]([NH:11][C:12]2[N:23]=[CH:22][CH:21]=[CH:20][C:13]=2[C:14]([NH:16][CH2:17][C:18]2[N:26]=[N:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([O:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH:29]=3)[CH:19]=2)=[O:15])[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 23667548Sodium AscorbateHCID 581200811-(Azidomethyl)-3-phenoxybenzeneHCID 1181260802-(3,5-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide

Product 1

HCID 906810052-(3,5-Dimethoxyphenylamino)-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)nicotinamideYield 78%

Reagents, catalysts & solvents

2
HCID 24462Copper SulfateCatalystHCID 6386tert-ButanolSolvent

Procedure

Compound 8 (194 mg, 1 mmol) and 3,5-dimethoxyaniline (91,153 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-(3,5-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide 10i as pure product. To a solution of 2-(3,5-dimethoxyphenylamino)-N-(prop-2-ynyl)nicotinamide (101,150 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 (0.005 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 1i (201 mg, 78%); mp: 123-125° C.; 1H NMR (300 MHz, CDCl3) δ 10.55 (s, 1H), 8.27 (dd, J=2.2, 1.5 Hz, 1H), 7.82 (dd, J=2.2, 1.5 Hz, 1H), 7.72 (t, J=6.0 Hz, 1H), 7.58 (s, 1H), 7.33-7.28 (m, 1H), 7.08 (t, J=7.5 Hz, 1H), 6.97-6.90 (m, 7H), 6.62-6.58 (m, 1H), 6.08 (t, J=2.2 Hz 1H), 5.46 (s, 2H), 4.61 (d, J=5.2 Hz, 2H), 3.80 ppm (s, 6H); MS (ESI m/z): 537 [M+H]+ Yield: 78%

Workup

  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

Sources & evidence

ORD record
ord-99ba171d88064d47b757cc6e524f3659
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09309225B2

Reaction notes

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