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

HRID 1726727

반응식

HRID 1726727 반응식
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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-6eff55a90b4547f190ac3275c0dfdad6
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07491741B2

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