Methanol → 1-Benzyl-4,7,10-tritosyl-1,4,7,10-tetraazacyclododecane

HRID 2259546Notes

Reaction equation

HRID 2259546 reaction equation
[H-].[Na+].[CH2:3]([N:10]([CH2:24][CH2:25][NH:26][S:27]([C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)(=[O:29])=[O:28])[CH2:11][CH2:12][NH:13][S:14]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[S:37]([C:41]1[CH:47]=[CH:46][C:44]([CH3:45])=[CH:43][CH:42]=1)([OH:40])(=[O:39])=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.S(C1C=CC(C)=CC=1)(O)(=O)=O.[NH:70]([CH2:74][CH2:75]O)[CH2:71][CH2:72]O.CO>CN(C)C=O>[CH2:3]([N:10]1[CH2:11][CH2:12][N:13]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:15])=[O:16])[CH2:75][CH2:74][N:70]([S:37]([C:41]2[CH:42]=[CH:43][C:44]([CH3:45])=[CH:46][CH:47]=2)(=[O:39])=[O:40])[CH2:71][CH2:72][N:26]([S:27]([C:30]2[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH2:25][CH2:24]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 3090868HCID 3090868, compoundHCID 86743555HCID 86743555, compound

Product 1

HCID 30908581-Benzyl-4,7,10-tritosyl-1,4,7,10-tetraazacyclododecaneYield 70.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Into a dry flask under nitrogen was placed about 3.9 g of a 60% sodium hydride dispersion. It was washed twice with hexanes then suspended in 200 ml of dry dimethylformamide. To the mixture was added 20 g (40 mmol) of 4-benzyl-1,7-bis-(p-toluenesulfonyl)-1,4,7-triazaheptane over 5 minutes. After the initial reaction had subsided, the mixture was heated to 110° C. for 1 hour. To the resulting hot solution was added dropwise 22.6 g (40 mmol) of diethanolamine tritosylate in 100 ml of dry dimethylformamide over 3.5 hours. After an additional 0.5 hours, the solution was allowed to cool and 20 ml of methanol was added. The volatiles were then removed on the rotary evaporator. The residue was dissolved in a mixture of 400 ml of water and 200 ml of dichloromethane. The phases were separated and the aqueous phase washed twice more with dichloromethane. The combined organic fractions were dried (magnesium sulfate), filtered, and evaporated to give a yellow oil. Crystallization was induced by the addition of about 100 ml of methanol. The mixture was kept at -5° C. overnight and the product collected by filtration. After drying, 20.4 g of a colorless solid was obtained; melting point 208°-210° C.

Workup

  1. customInto a dry flask under nitrogen was placed
  2. washIt was washed twice with hexanes
  3. customAfter the initial reaction
  4. temperatureto cool
  5. customThe volatiles were then removed on the rotary evaporator
  6. dissolutionThe residue was dissolved in a mixture of 400 ml of water and 200 ml of dichloromethane
  7. customThe phases were separated
  8. washthe aqueous phase washed twice more with dichloromethane
  9. dry with materialThe combined organic fractions were dried (magnesium sulfate)
  10. filtrationfiltered
  11. customevaporated
  12. customto give a yellow oil
  13. customCrystallization
  14. additionwas induced by the addition of about 100 ml of methanol
  15. waitThe mixture was kept at -5° C. overnight
  16. filtrationthe product collected by filtration
  17. customAfter drying

Sources & evidence

ORD record
ord-12ac5b973bd04a5fb012642213b2b942
Source dataset
uspto-grants-1995_12
Patent number
US05474756

Reaction notes

Loading…