Diisopropylethylamine → N-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-4-iodo-2-nitroaniline

HRID 706464Notes

Reaction equation

HRID 706464 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:11]=[N:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[C:5]([O:18][CH3:19])=[CH:4][C:3]=1[CH2:20][NH2:21].F[C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[N+:30]([O-:32])=[O:31].C(N(CC)C(C)C)(C)C>C(#N)C.O>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:11]=[N:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[C:5]([O:18][CH3:19])=[CH:4][C:3]=1[CH2:20][NH:21][C:23]1[CH:28]=[CH:27][C:26]([I:29])=[CH:25][C:24]=1[N+:30]([O-:32])=[O:31]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 145905821-Fluoro-4-iodo-2-nitrobenzeneHCID 118114007(2-Fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)phenyl)methanamine

Product 1

HCID 118113984N-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-4-iodo-2-nitroanilineYield 23.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)phenyl)methanamine (0.89 g, 3.04 mmol) in acetonitrile (15 mL) was added 1-fluoro-4-iodo-2-nitrobenzene (0.89 g, 3.35 mmol) and N,N-diisopropylethylamine. The resulting yellow solution was heated to reflux. After 16 h, the mixture was allowed to cool to room temperature and was diluted with water. The mixture was extracted with ethyl acetate (3×25 mL). The combined organic phases were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification (Combi-Flash, 40 g SiO2 column, 0-33% ethyl acetate/hexanes elute) afforded 0.38 g (23%) of N-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-4-iodo-2-nitroaniline as a solid.

Workup

  1. temperatureThe resulting yellow solution was heated to reflux
  2. extractionThe mixture was extracted with ethyl acetate (3×25 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customChromatographic purification (Combi-Flash, 40 g SiO2 column, 0-33% ethyl acetate/hexanes elute)

Sources & evidence

ORD record
ord-1f6bf05f81da48bba20c0aef7aa7cd73
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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