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

HRID 2374968Notes

Reaction equation

HRID 2374968 reaction equation
[NH2:1][CH:2]([C:4]1[N:9]=[N:8][C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[N:6][CH:5]=1)[CH3:3].[Br:19][C:20]1[S:24][C:23]([C:25](O)=[O:26])=[CH:22][CH:21]=1.C(N(CC)CC)C>CN(C)C=O>[NH3:1].[Br:19][C:20]1[S:24][C:23]([C:25]([NH:1][CH:2]([C:4]2[N:9]=[N:8][C:7]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:6][CH:5]=2)[CH3:3])=[O:26])=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 3491155-Bromothiophene-2-carboxylic acidHCID 587119996-(1-aminoethyl)-N-[4-(methyloxy)phenyl]-1,2,4-triazin-3-amine2×

Product 2

HCID 222AmmoniaHCID 587119305-bromo-N-[1-(3-{[4-(methyloxy)phenyl]amino}-1,2,4-triazin-6-yl)ethyl]-2-thiophenecarboxamideYield 122.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-(1-aminoethyl)-N-[4-(methyloxy)phenyl]-1,2,4-triazin-3-amine (Intermediate 47) (100 mg, 0.41 mmol), 5-bromothiophene-2-carboxylic acid (93 mg, 0.45 mmol) and O-(7-azabenzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophospahte (186 mg, 0.49 mmol) in N,N-dimethylformamide (5 mL) was added triethylamine (0.170 mL, 1.22 mmol) and the resulting mixture stirred at room temperature, under nitrogen, for 2 h 50 min. The mixture was then reduced under vacuum and the residue purified by SPE (Si, 10 g cartridge) eluting with hexane/ethyl acetate (10:1 to 0:1) and then methanol. The appropriate fractions containing product were combined and then purified further by SPE (SCX, 5 g cartridge) eluting with methanol then ammonia in methanol (0.5 N to 2.0 N) to afford 5-bromo-N-[1-(3-{[4-(methyloxy)phenyl]amino}-1,2,4-triazin-6-yl)ethyl]-2-thiophenecarboxamide (109 mg) as a yellow solid. MS m/z 434/436 (M+1).

Workup

  1. customthe residue purified by SPE (Si, 10 g cartridge)
  2. washeluting with hexane/ethyl acetate (10:1 to 0:1)
  3. additionThe appropriate fractions containing product
  4. custompurified further by SPE (SCX, 5 g cartridge)
  5. washeluting with methanol

Sources & evidence

ORD record
ord-721217452faf42569efdfb296688f546
Source dataset
uspto-grants-2008_12
Patent number
US07462614B2

Reaction notes

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