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

HRID 626375
Notes
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Reaction equation

HRID 626375 reaction equation
[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]=[CH:30][C:29]([F:32])=[CH:28][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>[F:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][N:22]2[CH:17]=[C:16]([CH2:15][NH:14][C:12](=[O:13])[C:11]3[CH:18]=[CH:19][CH:20]=[N:21][C:10]=3[NH:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:24]=[N:23]2)=[CH:27][CH:28]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 112058641-(Azidomethyl)-4-fluorobenzeneHCID 23667548Sodium AscorbateHCID 1181259512-(4-methoxyphenylamino)-N-(prop-2-ynyl)nicotinamide

Product 1

HCID 90681010N-((1-(4-Fluorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(4-methoxyphenylamino)nicotinamideYield 75.5%

Reagents, catalysts & solvents

2
HCID 24462Copper SulfateCatalystHCID 6386tert-ButanolSolvent

Procedure

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)-4-fluorobenzene (12b, 88 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 2e (173 mg, 75%); mp: 169-171° C.; 1H NMR (500 MHz, CDCl3) δ 10.26 (s, 1H), 8.23 (dd, J=4.0, 1.5 Hz, 1H), 7.74 (dd, J=8.0, 1.5 Hz, 1H), 7.50 (d, J=9.0 Hz, 1H), 7.29-7.24 (m, 4H), 7.06 (t, J=9.0 Hz, 2H), 6.83 (d, J=9.0 Hz, 2H), 6.59-6.50 (m, 1H), 5.47 (s, 2H), 4.64 (d, J=5.2 Hz, 2H), 3.78 (s, 3H); MS (ESI m/z): 433 [M+H]+. Yield: 75%

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-fe607d13065e41289a46ef43427a4bb9
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09309225B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes