Acetonitrile → HCID 68155976, compound

HRID 1877798Notes

Reaction equation

HRID 1877798 reaction equation
Cl.Cl.[CH3:3][C:4]([CH3:16])([CH2:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)[C:5]([O:7][CH3:8])=[O:6].[Cl:17][C:18]1[CH:19]=[CH:20][C:21]2[N:27]=[C:26](Cl)[C:25]3=[CH:29][C:30]([CH3:32])=[CH:31][N:24]3[CH2:23][C:22]=2[CH:33]=1.C(#N)C.C(=O)([O-])[O-].[K+].[K+]>O>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]2[N:27]=[C:26]([N:13]3[CH2:14][CH2:15][N:10]([CH2:9][C:4]([CH3:16])([CH3:3])[C:5]([O:7][CH3:8])=[O:6])[CH2:11][CH2:12]3)[C:25]3=[CH:29][C:30]([CH3:32])=[CH:31][N:24]3[CH2:23][C:22]=2[CH:33]=1

Participants

6

Reactant 4

HCID 6342Acetonitrile2×HCID 11430Potassium CarbonateHCID 68155933Methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate dihydrochlorideHCID 68156097HCID 68156097, compound

Product 1

HCID 68155976HCID 68155976, compoundYield 58.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

Dissolve methyl 2,2-dimethyl-3-(piperazin-1-yl)propanoate dihydrochloride (1.61 g, 5.89 mmoles) in water and load on to two SCX-2 (10 g) cartridges. Wash the cartridges with methanol and elute with 2M ammonia in methanol. Concentrate in vacuo, then dissolve the resultant oil in acetonitrile (40 mL). Add 7,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.167 g, 4.4 mmoles) to the acetonitrile solution. Divide the acetonitrile solution and place in to 2 microwave tubes, add potassium carbonate (0.89 g, 6.79 mmoles) to each microwave tube and heat and stir at 140° C. in the microwave for 3.5 hr. Allow the reaction mixture to cool, filter, wash the solid collected on the sinter with acetonitrile then concentrate the filtrate in vacuo, add methanol and then evaporate to dryness. Treat with more methanol and collect the resultant precipitate, wash the precipitate with methanol 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 as a crystalline solid (1.1 g). MS (m/z): 429.18 (M+1).

Workup

  1. washWash the cartridges with methanol
  2. washelute with 2M ammonia in methanol
  3. concentrationConcentrate in vacuo
  4. dissolutiondissolve the resultant oil in acetonitrile (40 mL)
  5. temperatureheat
  6. temperatureto cool
  7. filtrationfilter
  8. washwash the solid
  9. customcollected on the sinter with acetonitrile
  10. concentrationthen concentrate the filtrate in vacuo
  11. additionadd methanol
  12. customevaporate to dryness
  13. additionTreat with more methanol
  14. customcollect the resultant precipitate
  15. washwash the precipitate with methanol

Sources & evidence

ORD record
ord-b509904b731e44bd9bf83683cab1d429
Source dataset
uspto-grants-2012_11
Patent number
US08314092B2

Reaction notes

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