Ethylenediamine → HCID 46235938, compound

HRID 906031Notes

Reaction equation

HRID 906031 reaction equation
[C:1]([CH2:3][C:4]([N:6]1[CH2:11][CH2:10][CH2:9][CH:8]([NH:12][C:13]([NH:15][C:16]2[N:17]=[C:18]3[CH:24]=[CH:23][N:22](COCC[Si](C)(C)C)[C:19]3=[N:20][CH:21]=2)=[O:14])[CH2:7]1)=[O:5])#[N:2].F[B-](F)(F)F.[Li+].C(N)CN>O.C(#N)C>[C:1]([CH2:3][C:4]([N:6]1[CH2:11][CH2:10][CH2:9][CH:8]([NH:12][C:13]([NH:15][C:16]2[N:17]=[C:18]3[CH:24]=[CH:23][NH:22][C:19]3=[N:20][CH:21]=2)=[O:14])[CH2:7]1)=[O:5])#[N:2]

Participants

6

Reactant 3

HCID 3301EthylenediamineHCID 4298216Lithium tetrafluoroborateHCID 67385867HCID 67385867, compound

Product 1

HCID 46235938HCID 46235938, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
85 °C

Procedure

A mixture of 1-[1-(2-cyano-acetyl)-piperidin-3-yl]-3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea (0.09 g, 0.197 mmol) and lithium tetrafluoroborate (0.184 g, 1.967 mmol) in 2 mL of a 9/1 mixture of acetonitrile and H2O was stirred at 85° C. for 24 hours before being cooled to RT (almost no solvent left). The reaction mixture was diluted in 2 mL of a 9/1 mixture of acetonitrile and H2O, ethylenediamine (0.066 mL, 0.983 mmol) was added and the resulting mixture was stirred at RT for 3 hours before being evaporated. The residue was partitioned between EtOAc and saturated aqueous NaHCO3. The aqueous layer was back extracted twice with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and evaporated. The fairly insoluble residue was adsorbed onto silica purified by SiO2 flash chromatography (DCM/(DCM:MeOH:NH4OH 60:10:1] 90% to 0% DCM) to give 0.008 g of (1-[1-(2-cyano-acetyl)-piperidin-3-yl]-3-(5H-pyrrolo[2,3-b]pyrazin-2-yl)-urea (14% yield).

Workup

  1. temperaturebefore being cooled to RT (almost no solvent
  2. waitleft)
  3. additionwas added
  4. stirringthe resulting mixture was stirred at RT for 3 hours
  5. custombefore being evaporated
  6. customThe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  7. extractionThe aqueous layer was back extracted twice with EtOAc
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. custompurified by SiO2 flash chromatography (DCM/(DCM:MeOH:NH4OH 60:10:1] 90% to 0% DCM)

Sources & evidence

ORD record
ord-7898b73ded6f4a1aa12f1fdd70643cb6
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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