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 2053743ノート

反応式

HRID 2053743 の反応式
[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]

参加物

7

反応物 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

生成物 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]-methanone収率 76.3%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7952e2b1f82143d4889e4c2f104a996a
出典データセット
uspto-grants-2008_02
特許番号
US07326700B2

反応ノート

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