Methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate hydrochloride → HCID 22120220, compound

HRID 1877802Notes

Reaction equation

HRID 1877802 reaction equation
Cl.[CH3:2][C:3]([CH3:15])([CH2:8][N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)[C:4]([O:6][CH3:7])=[O:5]>CO>[CH3:2][C:3]([CH3:15])([CH2:8][N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)[C:4]([O:6][CH3:7])=[O:5]

Participants

3

Reactant 1

HCID 68156003Methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate hydrochloride

Product 1

HCID 22120220HCID 22120220, compoundYield 93.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Add phosphoryl chloride (5 equiv; 4.36 mL, 7.19 g, 46.89 mmoles) to 2,7-dichloro-5,10-dihydro-11H-pyrrolo[2,1-c][1,4]benzodiazepin-11-one (1 equiv; 2.505 g, 9.38 mmoles) in chloroform (80 mL) and heat and stir at 50° C. overnight. Decant the reaction solution and evaporate in vacuo to an oil. Dissolve the oil in DCM, wash with saturated aqueous sodium hydrogen carbonate solution. Dry the DCM solution over Na2SO4, filter and concentrate to dryness to give 2,7,11-trichloro-5H-pyrrolo[2,1-c][1,4]benzodiazepine as a cream colored solid. In parallel desalt methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate hydrochloride (0.837 g, 3.54 mmoles) by dissolving in methanol, add the methanolic solution to an SCX-2 column (10 g) wash with methanol and then elute with 2.5M ammonia in methanol solution, evaporate the methanol ammonia fraction to give methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate (0.665 g) as an oil. Mix this oil with 2,7,11-trichloro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.505 g 1.77 mmoles), potassium carbonate (0.733 g, 5.31 mmoles) and acetonitrile (20 mL) and heat at reflux overnight. Cool the reaction mixture to room temperature and filter, washing the sinter with EtOAc, then evaporate the filtrate in vacuo to a solid. Chromatograph on silica eluting with methanol/DCM (gradient elution 2:98 to 8:92). Evaporate the fractions containing product to give methyl 3-[4-(2,7-dichloro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoate (0.69 g). MS (m/z): 449.13/451.07 (M+1).

Workup

  1. additionadd the methanolic solution to an SCX-2 column (10 g)
  2. washwash with methanol
  3. washelute with 2.5M ammonia in methanol solution
  4. customevaporate the methanol ammonia fraction

Sources & evidence

ORD record
ord-ad0acf9347774ca19fe669d0227eeb98
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

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