Triethylamine → 10-Chloro-2-cyclopropyl-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one

HRID 2234412Notes

Reaction equation

HRID 2234412 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[Cl:5][C:6]1[N:11]=[C:10](Cl)[C:9]([N:13]([CH3:18])[C:14](=[O:17])[CH:15]=[CH2:16])=[CH:8][N:7]=1.C(N(CC)CC)C>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4].C(Cl)Cl>[Cl:5][C:6]1[N:7]=[C:8]2[C:9]([N:13]([CH3:18])[C:14](=[O:17])[CH2:15][CH2:16][N:4]2[CH:1]2[CH2:3][CH2:2]2)=[CH:10][N:11]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 69828CyclopropylamineHCID 86617580N-(2,4-dichloropyrimidin-5-yl)-N-methyl-prop-2-enamide2×

Product 1

HCID 8661758210-Chloro-2-cyclopropyl-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-oneYield 11.5%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 6344DichloromethaneSolvent

Procedure

Cyclopropylamine (Aldrich; 150 μL, 2.18 mmol), N-(2,4-dichloropyrimidin-5-yl)-N-methyl-prop-2-enamide (Intermediate 113; 337 mg, 1.45 mmol) Triethylamine (404 μL, 2.9 mmol), Titanium Tetra-ethoxide (152 μL, 0.725 mmol) and DCM (5 mL) were combined and stirred at room temp for 1 hr, heated at 40° C. for 4 hrs then cooled to room temperature. The reaction mixture was washed with water then gravity filtered through a PTFE cup, the aqueous layer containing the titanium emulsion was washed with further DCM (3×10 mL) and the combined organic solutions gravity filtered through a PTFE cup and solvents evaporated. The residue was dissolved in DCM and purified by chromatographic separation on silica eluting with a shallow gradient (25 column volumes) of 10-50% Ethyl Acetate/iso-hexane. Product containing fractions were combined and evaporated to give the title compound as a cream solid (42 mg, 11%)

Workup

  1. temperatureheated at 40° C. for 4 hrs
  2. temperaturethen cooled to room temperature
  3. washThe reaction mixture was washed with water
  4. filtrationgravity filtered through a PTFE cup
  5. additionthe aqueous layer containing the titanium emulsion
  6. washwas washed with further DCM (3×10 mL)
  7. filtrationthe combined organic solutions gravity filtered through a PTFE cup and solvents
  8. customevaporated
  9. dissolutionThe residue was dissolved in DCM
  10. custompurified by chromatographic separation on silica eluting with a shallow gradient (25 column volumes) of 10-50% Ethyl Acetate/iso-hexane
  11. additionProduct containing fractions
  12. customevaporated

Sources & evidence

ORD record
ord-73351dd812744197a09d6fd43285708a
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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