Triethylamine → 3-bromo-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide

HRID 2374880Notes

Reaction equation

HRID 2374880 reaction equation
[NH2:1][CH:2]([C:4]1[N:9]=[N:8][C:7]([NH:10][C:11]2[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=2)=[N:6][CH:5]=1)[CH3:3].[Br:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](O)=[O:28].C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[Br:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27]([NH:1][CH:2]([C:4]1[N:9]=[N:8][C:7]([NH:10][C:11]2[CH:12]=[C:13]([O:21][CH3:22])[C:14]([O:19][CH3:20])=[C:15]([O:17][CH3:18])[CH:16]=2)=[N:6][CH:5]=1)[CH3:3])=[O:28]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 114563-Bromobenzoic acidHCID 534044296-(1-aminoethyl)-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazin-3-amine2×

Product 1

HCID 587119543-bromo-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamideYield 74.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 6-(1-aminoethyl)-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazin-3-amine (Intermediate 9) (1.0 g, 3.3 mmol) in N,N-dimethylformamide (10 mL) was added 3-bromobenzoic acid (0.72 g, 3.6 mmol), O-(7-azabenzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophospahte (1.4 g, 3.6 mmol) and triethylamine (1.0 mL, 7.2 mmol). After stirring for 18 hours the solution was diluted with ethyl acetate (100 mL) and washed with 0.1 N HCl (2×100 mL) and saturated sodium bicarbonate solution (100 mL). The solution was dried with magnesium sulfate and filtered, and silica gel (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 (100:0) using a RediSep silica gel cartridge (40 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 3-bromo-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (1.2 g) as a white solid. 1H NMR (CDCl3): δ9.94(s, 1H), 9.05 (d, J=7.2 Hz, 1H), 8.53 (s, 1H), 8.10 (s, 1H), 7.89 (d, J=7.9 Hz, 1H), 7.73 (d, J=7.9 Hz, 1H), 7.43 (dd, J=8.0, 7.8 Hz, 1H), 7.19 (s, 2H), 5.29 (dd, J=7.2, 7.0 Hz, 1H), 3.75 (s, 6H), 3.61 (s, 3H), 1.59 (d, J=7.0 Hz, 3H). MS m/z 488, 500 (M+1, M+3).

Workup

  1. washwashed with 0.1 N HCl (2×100 mL) and saturated sodium bicarbonate solution (100 mL)
  2. dry with materialThe solution was dried with magnesium sulfate
  3. filtrationfiltered
  4. additionsilica gel (5 g) was added to the solution
  5. customfollowed by evaporation of the volatiles under reduced pressure
  6. washsubjected to a gradient elution
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5d6dff08e6474146b73588c6cf01997e
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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