Ethyl Acetate → HCID 11669602, compound

HRID 552322Notes

Reaction equation

HRID 552322 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([N:9]2[C:13]3=[N:14][C:15]([CH3:19])=[CH:16][C:17]([NH2:18])=[C:12]3[C:11]([CH3:20])=[CH:10]2)=[C:4]([CH3:21])[CH:3]=1.[C:22]([CH2:24][CH:25]([CH2:33][CH2:34]OS(C)(=O)=O)[CH2:26][CH2:27]OS(C)(=O)=O)#[N:23].C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>CN1CCCC1=O.O.CCCCCC>[Br:1][C:2]1[CH:3]=[C:4]([CH3:21])[C:5]([N:9]2[C:13]3=[N:14][C:15]([CH3:19])=[CH:16][C:17]([N:18]4[CH2:34][CH2:33][CH:25]([CH2:24][C:22]#[N:23])[CH2:26][CH2:27]4)=[C:12]3[C:11]([CH3:20])=[CH:10]2)=[C:6]([CH3:8])[CH:7]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 58281281HCID 58281281, compoundHCID 59843348HCID 59843348, compound2×

Product 1

HCID 11669602HCID 11669602, compoundYield 65.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-ylamine (10.0 g), methanesulfonic acid 3-cyanomethyl-5-methanesulfonyloxy-pentyl ester (11.3 g) and N,N-diisopropylethylamine (8.25 g) in N-methylpyrrolidone (10 mL) was heated at 135° C. for 4 hours. Methanesulfonic acid 3-cyanomethyl-5-methanesulfonyloxy-pentyl ester (2.60 g) was added to the reaction mixture and the mixture was heated at 135° C. for 4.5 hours. After cooling to room temperature, the reaction mixture was poured into a mixture of ethyl acetate, hexane and water (10/1/3), and separated. The aqueous phase was extracted with a mixture of ethyl acetate and hexane (10/1). The combined organic phase was washed with brine, dried over MgSO4, and filtered, and concentrated under reduced pressure. The residue was purified with column chromatography (silica gel: Wako gel C200, eluent: hexane:ethyl acetate:CHCl3=4/1/0.5) to obtain a solid. The solid was crystallized from diisopropylether to obtain {1-[1-(4-bromo-2,6-dimethyl-phenyl)-3,6-dimethyl-1H-pyrrolo[2,3-b]pyridin-4-yl]-piperidin-4-yl}-acetonitrile (8.61 g) as a solid.

Workup

  1. temperaturethe mixture was heated at 135° C. for 4.5 hours
  2. temperatureAfter cooling to room temperature
  3. customseparated
  4. extractionThe aqueous phase was extracted with a mixture of ethyl acetate and hexane (10/1)
  5. washThe combined organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified with column chromatography (silica gel: Wako gel C200, eluent: hexane:ethyl acetate:CHCl3=4/1/0.5)
  10. customto obtain a solid
  11. customThe solid was crystallized from diisopropylether

Sources & evidence

ORD record
ord-3956a0dbf0894c93bf9bc992141096c1
Source dataset
uspto-grants-2011_05
Patent number
US07951811B2

Reaction notes

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