1-Methylpiperazine → [10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepin-3-yl]-(4-methyl-piperazin-1-yl)-methanone

HRID 2053737Notes

Reaction equation

HRID 2053737 reaction equation
[C:1]1([C:7]2[CH:31]=[CH:30][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[C:24]([C:27](O)=[O:28])=[CH:25][CH:26]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][C:8]=2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[C:1]1([C:7]2[CH:31]=[CH:30][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[C:24]([C:27]([N:37]5[CH2:38][CH2:39][N:34]([CH3:33])[CH2:35][CH2:36]5)=[O:28])=[CH:25][CH:26]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][C:8]=2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

7

Reactant 5

HCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10113257HCID 10113257, compoundHCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 10118276[10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepin-3-yl]-(4-methyl-piperazin-1-yl)-methanoneYield 93.9%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Step E (0.200 g, 0.469 mmol), N-methyl piperazine (0.062 mL, 0.563 mmol), 1-hydroxy benzotriazole (0.070 g, 0.516 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.099 g, 0.516 mmol) were combined in amine-free N,N-dimethylformamide (1.9 mL), followed by the addition of N,N-diisopropylethyl amine (0.123 mL, 0.704 mmol). The reaction was stirred at room temperature for 12 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 combined organic phases were dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 5% methanol in chloroform to afford 0.224 g of the title compound as an oil. The oil thus obtained was dissolved in diethyl ether and diluted with hexane to afford a pale yellow solid.

Workup

  1. washwashed with water, saturated aqueous sodium bicarbonate, and brine
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel eluting with 5% methanol in chloroform

Sources & evidence

ORD record
ord-b79f253c270f416dae86a3eabc4a95b8
Source dataset
uspto-grants-2008_02
Patent number
US07326700B2

Reaction notes

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