Triethylamine → HCID 58711992, compound

HRID 2374861Notes

Reaction equation

HRID 2374861 reaction equation
Cl.[CH3:2][S:3][C:4]1[N:5]=[N:6][C:7]([CH:10]([NH2:12])[CH3:11])=[CH:8][N:9]=1.[Br:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18].N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[Br:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([NH:12][CH:10]([C:7]1[N:6]=[N:5][C:4]([S:3][CH3:2])=[N:9][CH:8]=1)[CH3:11])=[O:18]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 114563-Bromobenzoic acidHCID 4641409(Dimethylamino)-N,N-dimethyl(3H-(1,2,3)triazolo(4,5-b)pyridin-3-yloxy)methaniminiumHCID 68870503HCID 68870503, compound2×

Product 1

HCID 58711992HCID 58711992, compoundYield 83.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 1-[3-(methylthio)-1,2,4-triazin-6-yl]ethanamine hydrochloride (Intermediate 4) (10 g, 49 mmol) in N,N-dimethylformamide (100 mL) was added 3-bromobenzoic acid (11 g, 54 mmol), O-(7-azabenzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophospahte (20 g, 52 mmol) and triethylamine (24 mL, 170 mmol). After stirring for 18 hours the solution was concentrated under reduced pressure to approximately 50 mL. The solution was diluted with ethyl acetate (200 mL) and washed with 0.1N HCl (2×100 mL) and saturated sodium bicarbonate solution (100 mL). The solution was dried with magnesium sulfate and filtered, and silica gel (25 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 (0:100) to ethyl acetate:hexanes (40:60) using a RediSep silica gel cartridge (120 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 3-bromo-N-{1-[3-(methylthio)-1,2,4-triazin-6-yl]ethyl}benzamide (14.5 g) as a white solid. 1H NMR (CDCl3): δ8.47(s, 1H), 7.95 (dd, J=1.8, 1.7 Hz, 1H), 7.72 (ddd, J=7.9, 1.6, 1.1 Hz, 1H), 7.64 (ddd, J=7.9, 2.0, 1.1 Hz, 1H), 7.32 (dd, J=8.0, 7.7 Hz, 1H), 7.20 (d, J=7.2 Hz, 1H), 5.47 (dq, J=7.2, 7.0 Hz, 1H), 2.68 (s, 3H), 1.70 (d, J=7.0 Hz, 3H). MS m/z 353, 355 (M+1, M+3).

Workup

  1. concentrationwas concentrated under reduced pressure to approximately 50 mL
  2. additionThe solution was diluted with ethyl acetate (200 mL)
  3. washwashed with 0.1N HCl (2×100 mL) and saturated sodium bicarbonate solution (100 mL)
  4. dry with materialThe solution was dried with magnesium sulfate
  5. filtrationfiltered
  6. additionsilica gel (25 g) was added to the solution
  7. customfollowed by evaporation of the volatiles under reduced pressure
  8. washsubjected to a gradient elution
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2a68fa317ed24dd79d8f5c99cc6f3f85
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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