5-Ethylsulphonyl-o-anisidine → 3-bromo-N-[1-(3-{[5-(ethylsulfonyl)-2-methoxyphenyl]amino}-1,2,4-triazin-6-yl)ethyl]benzamide

HRID 2374890Notes

Reaction equation

HRID 2374890 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([NH:7][CH:8]([C:10]1[N:15]=[N:14][C:13](S(C)(=O)=O)=[N:12][CH:11]=1)[CH3:9])=[O:6].[CH2:23]([S:25]([C:28]1[CH:29]=[CH:30][C:31]([O:35][CH3:36])=[C:32]([CH:34]=1)[NH2:33])(=[O:27])=[O:26])[CH3:24].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[C:5]([NH:7][CH:8]([C:10]1[N:15]=[N:14][C:13]([NH:33][C:32]2[CH:34]=[C:28]([S:25]([CH2:23][CH3:24])(=[O:26])=[O:27])[CH:29]=[CH:30][C:31]=2[O:35][CH3:36])=[N:12][CH:11]=1)[CH3:9])=[O:6]

Participants

5

Reactant 3

HCID 792785-Ethylsulphonyl-o-anisidineHCID 521998p-Toluenesulfonic acid monohydrateHCID 58711953HCID 58711953, compound2×

Product 1

HCID 587120043-bromo-N-[1-(3-{[5-(ethylsulfonyl)-2-methoxyphenyl]amino}-1,2,4-triazin-6-yl)ethyl]benzamideYield 34.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-bromo-N-{1-[3-(methylsulfonyl)-1,2,4-triazin-6-yl]ethyl}benzamide (Intermediate 6) (240 mg, 0.62 mmol) in tetrahydrofuran (10 mL) was added 5-(ethylsulfonyl)-2-methoxyaniline (270 mg, 1.2 mmol) and 4-toluenesulfonic acid monohydrate (20 mg). After stirring for 24 hours, silica gel (2.5 g) was added to the solution, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexane (20:80) to ethyl acetate:hexanes (80:20) using a RediSep silica gel cartridge (12 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 3-bromo-N-[1-(3-{[5-(ethylsulfonyl)-2-methoxyphenyl]amino}-1,2,4-triazin-6-yl)ethyl]benzamide (110 mg) as a white solid. 1H NMR (CDCl3): δ9.00 (d, J=2.2 Hz, 1H), 8.44 (s, 1H), 8.03 (s, 1H), 7.95 (dd, J=1.9, 1.4 Hz, 1H), 7.72 (d, J=8.5 Hz, 1H), 7.62 (d, J=7.4 Hz, 1H), 7.57-7.52 (m, 1H), 7.22 (dd, J=8.1, 7.7 Hz, 1H) 7.00 (d, J=8.8 Hz, 1H) 5.44 (dq, J=7.2, 7.0 Hz, 1H), 3.98 (s, 3H), 3.10 (q, J=7.3 Hz, 2H), 1.68 (d, J=7.0 Hz, 3H), 1.24 (t, J=7.3 Hz, 3H). MS m/z 520, 522 (M+1, M+3).

Workup

  1. additionsilica gel (2.5 g) was added to the solution
  2. customfollowed by evaporation of the volatiles under reduced pressure
  3. washsubjected to a gradient elution
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c0c799ab3335483fa005717650819564
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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