Triethylamine → 10-Chloro-6-methyl-2-(1-methyl-4-piperidyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one

HRID 2234413Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2234413
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[Cl:9][C:10]1[N:15]=[C:14](Cl)[C:13]([N:17]([CH3:22])[C:18](=[O:21])[CH:19]=[CH2:20])=[CH:12][N:11]=1.C(N(CC)CC)C>[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4].C(Cl)Cl>[Cl:9][C:10]1[N:11]=[C:12]2[C:13]([N:17]([CH3:22])[C:18](=[O:21])[CH2:19][CH2:20][N:1]2[CH:2]2[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]2)=[CH:14][N:15]=1

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 27375314-Amino-1-methylpiperidineHCID 86617580N-(2,4-dichloropyrimidin-5-yl)-N-methyl-prop-2-enamide2×

Produkt 1

HCID 8661754610-Chloro-6-methyl-2-(1-methyl-4-piperidyl)-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-oneAusbeute 8,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 76524Titanium tetraethoxideKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-Amino-1-methylpiperidine (Fluorochem; 200 mg, 1.74 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 3 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 0-5% 2M ammonia in MeOH/DCM. Product containing fractions were combined and evaporated to give the title compound as a yellow solid (39 mg)

Aufarbeitung

  1. temperatureheated at 40° C. for 3 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 0-5% 2M ammonia in MeOH/DCM
  11. additionProduct containing fractions
  12. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-16099c5fc19d4105b1e06fa23bd82315
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07709471B2

Notizen zur Reaktion

Wird geladen…