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

HRID 1352016

Reaktionsgleichung

Reaktionsgleichung von HRID 1352016
C(N(C(C)C)CC)(C)C.[Br:10][C:11]1[CH:16]=[C:15]([C:17]([O-:19])=O)[CH:14]=[CH:13][C:12]=1[C:20]([O:22][CH3:23])=[O:21].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.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.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O>[Br:10][C:11]1[CH:16]=[C:15]([C:17]([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:19])[CH:14]=[CH:13][C:12]=1[C:20]([O:22][CH3:23])=[O:21]

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 226614481H-indole-4-methanamine hydrochlorideHCID 857711401,4-Benzenedicarboxylic acid, 2-bromo-, 1-methyl ester

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Diisopropylethylamine (2.3 mL, 13.2 mmol) was added dropwise to a solution of 2-bromo-1,4-benzenedicarboxylic acid, 1-methyl ester (Example 2; 861 mg, 3.32 mmol), HBTU (1.39 g, 3.65 mmol), 1H-indole-4-methanamine hydrochloride salt (Example 11; 528 mg, 3.98 mmol), and HOBT (493 mg, 3.65 mmol) in N,N-dimethylformamide (6.5 mL) at 0° C. The solution warmed to room temperature and stirred for 24 h. The solvent was concentrated under vacuum to remove most of the N,N-dimethylformamide. The residue was diluted with ethyl acetate (50 mL) and washed with 1 M HCl (10 mL), water (10 mL), saturated aqueous NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried (MgSO4), filtered, evaporated and flash chromatographed (silica, 25–35% ethyl acetate/petroleum ether) to give 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid, methyl ester (900 mg, 70%) as an off-white solid.

Aufarbeitung

  1. concentrationThe solvent 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 1 M HCl (10 mL), water (10 mL), saturated aqueous NaHCO3 (10 mL) and brine (10 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customflash chromatographed (silica, 25–35% ethyl acetate/petroleum ether)

Quellen und Nachweise

ORD-Eintrag
ord-e68f4e1f448d41b49c8160efb0713694
Quelldatensatz
uspto-grants-2007_05
Patentnummer
US07217728B2

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