Ethylenediamine → HCID 78132840, compound

HRID 2409084Notes

Reaction equation

HRID 2409084 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[CH:15]=[CH:14][N:13]=[C:12]([N:16]([CH2:36][CH3:37])[CH:17]([C:19]4[N:20]=[CH:21][C:22]5[N:27](COCC[Si](C)(C)C)[CH:26]=[CH:25][C:23]=5[N:24]=4)[CH3:18])[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.C(N)CN.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>CN(C=O)C>[N:24]1[C:23]2[CH:25]=[CH:26][NH:27][C:22]=2[CH:21]=[N:20][C:19]=1[CH:17]([N:16]([CH2:36][CH3:37])[C:12]1[N:11]=[C:10]([NH:9][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[NH:8][N:7]=2)[CH:15]=[CH:14][N:13]=1)[CH3:18]

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 8857Ethyl AcetateHCID 2724141Tetrabutylammonium FluorideHCID 86762630HCID 86762630, compound

Product 1

HCID 78132840HCID 78132840, compoundYield 64.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-ethyl-N2-(1-(5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl)ethyl)pyrimidine-2,4-diamine (103.9 mg, 0.20 mmol) in anhydrous DMF (4.7 mL) was added ethylenediamine (0.10 mL, 1.60 mmol) followed by tetrabutylammonium fluoride (1M in THF, 0.60 mL, 0.60 mmol), and the reaction mixture was stirred at 80° C. under N2 for 20 h. The reaction mixture was poured into EtOAc, and the organic layer was washed with 10% aq. NaOH solution, water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by SiO2 chromatography to afford 50.4 mg (64.7%) of racemic N2-(1-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)ethyl)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-ethylpyrimidine-2,4-diamine. Chiral SFC chromatography of racemic N2-(1-(5H-pyrrolo[3,2-d]pyrimidin-2-yl)ethyl)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-ethylpyrimidine-2,4-diamine (50.4 mg, 0.13 mmol) afforded the corresponding two enantiomers:

Workup

  1. washthe organic layer was washed with 10% aq. NaOH solution, water and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-c58693a858e340a18cdee2b65261a369
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

Loading…