Potassium Carbonate → HCID 68155976, compound

HRID 1877799Notes

Reaction equation

HRID 1877799 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10](Cl)[C:9]3=[CH:13][C:14]([CH3:16])=[CH:15][N:8]3[CH2:7][C:6]=2[CH:17]=1.Cl.[CH3:19][C:20]([CH3:32])([CH2:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)[C:21]([O:23][CH3:24])=[O:22].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([N:29]3[CH2:28][CH2:27][N:26]([CH2:25][C:20]([CH3:32])([CH3:19])[C:21]([O:23][CH3:24])=[O:22])[CH2:31][CH2:30]3)[C:9]3=[CH:13][C:14]([CH3:16])=[CH:15][N:8]3[CH2:7][C:6]=2[CH:17]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 68156003Methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate hydrochlorideHCID 68156097HCID 68156097, compound

Product 1

HCID 68155976HCID 68155976, compoundYield 97.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 7,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine (34.0 g, 128.23 mmoles) in acetonitrile (300 mL) add methyl 2,2-dimethyl-3-(piperazin-1-yl)-propionate hydrochloride (2.1 equiv; 63.75 g, 269.29 mmoles) and potassium carbonate (4 equiv; 70.89 g, 512.93 mmoles). Heat the mixture at reflux overnight. Evaporate to dryness. Partition the residue between water (500 mL) and EtOAc (2×500 mL). Combine the organic layers and wash with water (500 mL) then brine. Dry over sodium sulfate, filter and evaporate to a brown oil. Add iso-hexane (˜150 mL) and a seed crystal of Preparation 50. Allow to crystallize over 2 h, then transfer the flask to a fridge and allow to stand. Collect the resulting heavy crystalline solid by filtration, washing with cold iso-hexane. Dry in a vacuum oven at 40° C. for 1 h, to give methyl 3-[4-(7-chloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepin-11-yl)piperazin-1-yl]-2,2-dimethylpropanoate (53.6 g, 97% yield). MS (m/z): 429.18 (M+1).

Workup

  1. temperatureHeat the mixture
  2. temperatureat reflux overnight
  3. customEvaporate to dryness
  4. customPartition the residue between water (500 mL) and EtOAc (2×500 mL)
  5. washCombine the organic layers and wash with water (500 mL)
  6. dry with materialDry over sodium sulfate
  7. filtrationfilter
  8. customevaporate to a brown oil
  9. customAdd iso-hexane (˜150 mL) and a seed crystal of Preparation 50
  10. customAllow to crystallize over 2 h
  11. customCollect the resulting heavy crystalline solid
  12. filtrationby filtration
  13. washwashing with cold iso-hexane
  14. customDry in a vacuum oven at 40° C. for 1 h

Sources & evidence

ORD record
ord-364366ad2ec347fbac059356986cf227
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

Loading…