Cesium carbonate → 10-Chloro-6-methyl-2-(2-methylpropyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one

HRID 2234390Notes

Reaction equation

HRID 2234390 reaction equation
Br[C:2]1[C:3]([N:9]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH2:10][CH2:11][C:12]([NH:14][CH3:15])=[O:13])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:5]1[N:4]=[C:3]2[C:2]([N:14]([CH3:15])[C:12](=[O:13])[CH2:11][CH2:10][N:9]2[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866175693-[(5-bromo-2-chloro-pyrimidin-4-yl)-(2-methylpropyl)amino]-N-methyl-propanamide2×

Product 1

HCID 8661754410-Chloro-6-methyl-2-(2-methylpropyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-oneYield 41%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-[(5-bromo-2-chloro-pyrimidin-4-yl)-(2-methylpropyl)amino]-N-methyl-propanamide (Intermediate 85; 3.26 g, 9.32 mmol)) was suspended in dioxane (70 mL), Caesium Carbonate (6 g, 18.64 mmol) was added and the mixture bubbled with nitrogen for 10 minutes. Tris(dibenzylideneacetone)dipalladium(0) (512 mg, 0.56 mmol) and XANTPHOS (485 mg, 0.839 mmol) were added and the mixture heated at 100° C. for 24 hrs. The reaction mixture was cooled to room temperature, solvent evaporated and the residues partitioned between DCM (250 mL) and water (250 mL). The aqueous phase was re-extracted with DCM (200 mL) and the combined organic phases dried over MgSO4 and evaporated to a dark brown gum which was taken up in DCM and purified on silica, eluting with a gradient of 30-50% Ethyl Acetate/iso-hexane then 50% Ethyl Acetate/iso-hexane. Fractions containing product were combined and evaporated to a yellow solid, which was heated at reflux in iso-hexane (50 mL) for 15 minutes and allowed to cool to room temperature overnight. The resulting solid was filtered and dried to give the title compound as a pale yellow solid (1.02 g, 41%)

Workup

  1. customthe mixture bubbled with nitrogen for 10 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customsolvent evaporated
  4. customthe residues partitioned between DCM (250 mL) and water (250 mL)
  5. extractionThe aqueous phase was re-extracted with DCM (200 mL)
  6. dry with materialthe combined organic phases dried over MgSO4
  7. customevaporated to a dark brown gum which
  8. custompurified on silica
  9. washeluting with a gradient of 30-50% Ethyl Acetate/iso-hexane
  10. additionFractions containing product
  11. customevaporated to a yellow solid, which
  12. temperaturewas heated
  13. temperatureat reflux in iso-hexane (50 mL) for 15 minutes
  14. temperatureto cool to room temperature overnight
  15. filtrationThe resulting solid was filtered
  16. customdried

Sources & evidence

ORD record
ord-bc96a185353d40ce80d7956e9e0ddb0e
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

Loading…