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

HRID 393018

反応式

HRID 393018 の反応式
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]

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 226614481H-indole-4-methanamine hydrochlorideHCID 857711401,4-Benzenedicarboxylic acid, 2-bromo-, 1-methyl ester

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 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.

後処理

  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)

出典と根拠

ORDレコード
ord-4a03e3814f6c4d77a9c3ae90afd96f4b
出典データセット
uspto-grants-2004_10
特許番号
US06803384B2

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