1-Hydroxybenzotriazole → 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl ester

HRID 1058386Notes

Reaction equation

HRID 1058386 reaction equation
C(N(C(C)C)CC)(C)C.[Br:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=1[C:20]([O:22][CH3:23])=[O:21])[C:14]([OH:16])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.Cl.[NH:49]1[C:57]2[CH:56]=[CH:55][CH:54]=[C:53]([CH2:58][NH2:59])[C:52]=2[CH:51]=[CH:50]1.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[CH3:23][O:22][C:20](=[O:21])[C:19]1[CH:18]=[CH:17][C:13]([C:14]([NH:59][CH2:58][C:53]2[CH:54]=[CH:55][CH:56]=[C:57]3[C:52]=2[CH:51]=[CH:50][NH:49]3)=[O:16])=[CH:12][C:11]=1[Br:10]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 186730263-Bromo-4-(methoxycarbonyl)benzoic acidHCID 226614481H-indole-4-methanamine hydrochloride

Product 1

HCID 235607692-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl esterYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Diisopropylethylamine (2.3 mL, 13.2 mmol) was added dropwise to a solution of 3-bromo-4-(methoxycarbonyl)benzoic acid (Example 76; 861 mg, 3.32 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.39 g, 3.65 mmol), 1H-indole-4-methanamine hydrochloride salt (Example 68; 528 mg, 3.98 mmol) and 1-hydroxybenzotriazole (493 mg, 3.65 mmol) in N,N-dimethylformamide (6.5 mL) at 0° C. The solution was allowed to warm to room temperature and then was stirred for 24 h. After the reaction mixture was concentrated under vacuum to remove most of the N,N-dimethylformamide, the residue was diluted with ethyl acetate (50 mL) and washed with 1N hydrochloric acid solution (10 mL), water (10 mL), saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL). The organic layer was dried (MgSO4), filtered, evaporated and the residue was chromatographed (silica gel, 25-35% ethyl acetate in petroleum ether) to provide 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl ester (900 mg, 70% yield) as an off-white solid.

Workup

  1. concentrationAfter the reaction mixture was concentrated under vacuum
  2. customto remove most of the N,N-dimethylformamide
  3. additionthe residue was diluted with ethyl acetate (50 mL)
  4. washwashed with 1N hydrochloric acid solution (10 mL), water (10 mL), saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was chromatographed (silica gel, 25-35% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-792d381c9b9a4638b183402f2afa81c2
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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