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

HRID 1058386

反応式

HRID 1058386 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-792d381c9b9a4638b183402f2afa81c2
出典データセット
uspto-grants-2003_02
特許番号
US06515124B2

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