Ethylenediamine → HCID 178453646, compound

HRID 1969629Notes

Reaction equation

HRID 1969629 reaction equation
C(N)CN.[C:5]([O:9][C:10](=[O:42])[NH:11][CH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([NH:19][C:20]([C:22]2[C:30]3[N:29]4[CH:31]=[N:32][N:33]=[C:28]4[CH:27]=[N:26][C:25]=3[N:24](COCC[Si](C)(C)C)[CH:23]=2)=[O:21])[CH2:15][CH2:14]1)([CH3:8])([CH3:7])[CH3:6].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:5]([O:9][C:10](=[O:42])[NH:11][CH2:12][C@H:13]1[CH2:14][CH2:15][C@H:16]([NH:19][C:20]([C:22]2[C:30]3[N:29]4[CH:31]=[N:32][N:33]=[C:28]4[CH:27]=[N:26][C:25]=3[NH:24][CH:23]=2)=[O:21])[CH2:17][CH2:18]1)([CH3:8])([CH3:6])[CH3:7]

Participants

5

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium FluorideHCID 178453645HCID 178453645, compound

Product 1

HCID 178453646HCID 178453646, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Ethylenediamine (0.011 mL, 0.16 mmol) was added to a solution of tert-butyl(trans-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-8-carboxamido)cyclohexyl)methylcarbamate (0.043 g, 0.079 mmol, prepared using Z from Preparation #AAAAA.1 and KOH, H with tert-butyl trans-4-aminocyclohexylmethylcarbamate [AMRI], HATU, and TEA) in THF (1 mL). TBAF (1.0 M solution in THF, 0.470 mL, 0.470 mmol) was added in one portion. The mixture was heated at about 60° C. After about 24 h, the solution was allowed to cool to ambient temperature and stirred for about 40 h. The volatiles were removed under reduced pressure. The residue was slurried in water (10 mL) and extracted with EtOAc (4×20 mL). The combined organic portions were washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 2-10% MeOH/DCM to give tert-butyl(trans-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine-8-carboxamido)cyclohexyl)methylcarbamate (0.0094 g, 29%): LC/MS (Table 1, Method n) Rt=0.55 min; MS m/z: 414 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. customThe volatiles were removed under reduced pressure
  3. extractionextracted with EtOAc (4×20 mL)
  4. washThe combined organic portions were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of 2-10% MeOH/DCM

Sources & evidence

ORD record
ord-4fe588cb2aed4e45b2ec051d3cf0e0fd
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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