Cesium carbonate → 1-cyclohexyl-3-[7-isopropenyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea

HRID 906007Notes

Reaction equation

HRID 906007 reaction equation
[CH:1]1([NH:7][C:8]([NH:10][C:11]2[N:12]=[C:13]3[C:19](I)=[CH:18][N:17]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]3=[N:15][CH:16]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:29](B1OC(C)(C)C(C)(C)O1)([CH3:31])=[CH2:30].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.O>[CH:1]1([NH:7][C:8]([NH:10][C:11]2[N:12]=[C:13]3[C:19]([C:29]([CH3:31])=[CH2:30])=[CH:18][N:17]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:14]3=[N:15][CH:16]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 673859971-cyclohexyl-3-[7-iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea

Product 1

HCID 673856211-cyclohexyl-3-[7-isopropenyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-ureaYield 52.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Cyclohexyl-3-[7-iodo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea (300 mg, 0.582 mmol), 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.33 mL, 1.75 mmol), Cs2CO3 (948 mg, 2.91 mmol), and Pd(dppf)Cl2 DCM complex (47 mg, 0.058 mmol) were dissolved in THF (2.3 mL) and H2O (0.7 mL). The mixture was irradiated at 100° C. using microwave for 1 hr, cooled to RT, partitioned between EtOAc and brine. The organic layer was dried (MgSO4), filtered, concentrated, and purified by SiO2 chromatography (24 g SiO2, DCM/MeOH 0 to 5% MeOH) to give 131 mg of impure 1-cyclohexyl-3-[7-isopropenyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-urea as an off-white solid (52% yield).

Workup

  1. customThe mixture was irradiated at 100° C.
  2. customfor 1 hr
  3. custompartitioned between EtOAc and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by SiO2 chromatography (24 g SiO2, DCM/MeOH 0 to 5% MeOH)

Sources & evidence

ORD record
ord-5e8be35cd0264374b9611f88afd7edb5
Source dataset
uspto-grants-2011_09
Patent number
US08012974B2

Reaction notes

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