1-Methylpiperazine → [4-(3-Hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-phenyl]-[3-(4-methyl-piperazine-1-carbonyl)-10,11-dihydro-5h-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]-methanone

HRID 2053743노트

반응식

HRID 2053743 반응식
[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][C:4]([C:8]2[CH:32]=[CH:31][C:11]([C:12]([N:14]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[CH2:18][N:17]4[C:25]([C:28](O)=[O:29])=[CH:26][CH:27]=[C:16]4[CH2:15]3)=[O:13])=[CH:10][C:9]=2[CH3:33])=[C:3]1[CH3:34].[CH3:35][N:36]1CCNC[CH2:37]1.ON1C2C=CC=CC=2N=N1.Cl.[CH2:53]([N:55]=[C:56]=N)[CH3:54].C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][C:4]([C:8]2[CH:32]=[CH:31][C:11]([C:12]([N:14]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[CH2:18][N:17]4[C:25]([C:28]([N:55]5[CH2:53][CH2:54][N:36]([CH3:37])[CH2:35][CH2:56]5)=[O:29])=[CH:26][CH:27]=[C:16]4[CH2:15]3)=[O:13])=[CH:10][C:9]=2[CH3:33])=[C:3]1[CH3:34]

참가 물질

7

반응물 5

HCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1027608810-[4-(3-Hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-benzoyl]-10,11-dihydro-5h-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acidHCID 21883477Ethylcarbodiimide hydrochloride

생성물 1

HCID 10119604[4-(3-Hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-phenyl]-[3-(4-methyl-piperazine-1-carbonyl)-10,11-dihydro-5h-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]-methanone수율 76.3%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

10-[4-(3-hydroxy-2-methyl-cyclohex-1-en-1-yl)-3-methyl-benzoyl]-10,11-dihydro-5H pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid (0.200 g, 0.438 mmol) of Step A, N-methylpiperazine (0.058 mL, 0.526 mmol), 1-hydroxy benzotriazole (0.065 g, 0.482 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.092 g, 0.482 mmol) were combined in amine-free N,N-dimethylformamide (1.8 mL), followed by addition of N,N-diisopropylethyl amine (0.114 mL, 0.657 mmol). The reaction was stirred at room temperature for 18 hours, then diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate, and brine. The combined aqueous washings were saturated with sodium chloride and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel using a solvent gradient from 0 to 8% of methanol in chloroform to afford 0.180 g of the title compound as a white solid.

후처리

  1. washwashed with water, saturated aqueous sodium bicarbonate, and brine
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel using a solvent gradient from 0 to 8% of methanol in chloroform

출처 및 근거

ORD 기록
ord-7952e2b1f82143d4889e4c2f104a996a
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07326700B2

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