Methylamine → 3-cyclohexyl-1-methyl-1-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea

HRID 905984Notes

Reaction equation

HRID 905984 reaction equation
BrC1N=C2C=CN(COCC[Si](C)(C)C)C2=NC=1.CN.[CH3:21][NH:22][C:23]1[N:24]=[C:25]2[CH:31]=[CH:30][N:29]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:26]2=[N:27][CH:28]=1.[CH:40]1([N:46]=[C:47]=[O:48])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>CS(C)=O.ClCCCl>[CH:40]1([NH:46][C:47](=[O:48])[N:22]([CH3:21])[C:23]2[N:24]=[C:25]3[CH:31]=[CH:30][N:29]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:26]3=[N:27][CH:28]=2)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 18502Cyclohexyl isocyanateHCID 575165972-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazineHCID 67385648Methyl-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-amine

Product 1

HCID 673853353-cyclohexyl-1-methyl-1-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-ureaYield 27%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
150 °C

Procedure

2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine (0.328 g, 1.00 mmol) was dissolved in DMSO (2.5 mL). A solution of methylamine (33 wt % in EtOH, 2.5 mL, 20 mmol) was added and the resulting solution was heated at 150° C. in the sealed tube overnight, then cooled to RT. The reaction mixture was partitioned between EtOAc and H2O. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated to give a mixture of impure Methyl-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-amine, which was dissolved in 1,2-dichloroethane (3 mL). Cyclohexylisocyanate (0.38 mL, 3.00 mmol) was added and the reaction mixture was heated to reflux overnight, cooled to RT, concentrated, purified by SiO2 chromatography (12 g SiO2, hexanes/EtOAc 0-35% EtOAc) to give 0.110 g of 3-cyclohexyl-1-methyl-1-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea as a yellow solid (27% yield).

Workup

  1. temperaturecooled to RT
  2. customThe reaction mixture was partitioned between EtOAc and H2O
  3. extractionThe aqueous layer was extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give
  9. temperaturethe reaction mixture was heated
  10. temperatureto reflux overnight
  11. temperaturecooled to RT
  12. concentrationconcentrated
  13. custompurified by SiO2 chromatography (12 g SiO2, hexanes/EtOAc 0-35% EtOAc)

Sources & evidence

ORD record
ord-148ccf897ce640e9b01e79cdb2bab415
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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