HCID 86749670, compound → HCID 19360710, compound

HRID 1736622Notes

Reaction equation

HRID 1736622 reaction equation
[N+:1]([C:4]1[CH:73]=[CH:72][C:7]([CH2:8][CH:9]([N:22](S(C2C=CC=CC=2C)(=O)=O)[CH2:23][CH2:24][N:25](S(C2C=CC=CC=2C)(=O)=O)[CH2:26][CH2:27][N:28](S(C2C=CC=CC=2C)(=O)=O)[CH2:29][CH2:30][NH:31]S(C2C=CC=CC=2C)(=O)=O)COS(C2C=CC=CC=2C)(=O)=O)=[CH:6][CH:5]=1)([O-:3])=[O:2]>CN(C=O)C>[N+:1]([C:4]1[CH:73]=[CH:72][C:7]([CH:8]2[CH2:9][NH:22][CH2:23][CH2:24][NH:25][CH2:26][CH2:27][NH:28][CH2:29][CH2:30][NH:31]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

3

Reactant 1

HCID 86749670HCID 86749670, compound2×

Product 1

HCID 19360710HCID 19360710, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The intramolecular cyclization step undertaken to give 2-(p-nitrobenzyl)-N,N',N", N"'-tetrakis (tolylsulfonyl)-1,4,7,10-tetraazacyclododecane is performed by treating 2-(p-nitrobenzyl)-N,N',N",N"',O-pentakis(tolylsulfonyl)-3,6,9,12-tetraaz-adodecanol with 1 equivalent of CsCO3 in DMF under high dilution conditions (0.01M of 2-(p-nitrobenzyl)-N,N',N",N"',O-pentakis(tolylsulfonyl)-3,6,9,12-tetraaza-dodecanol) at 60° C. for 5 hours under nitrogen. The tosyl protecting groups of 2-(p-nitrobenzyl)-N,N',N",N"'-tetrakis (tolylsulfonyl)-1,4,7,10-tetraazacyclododecane are removed using concentrated H2SO4 at 100° C. for 56 hours, affording 2-(p-nitrophenyl)-1,4,7,10-tetraaza-cyclododecane. 2-(p-nitrophenyl)-1,4,7,10-tetraaza-cyclododecane is treated with 4.4 equivalents of bromoacetic acid in water at pH 10 at 70° C. for one day to give crude product. The product p-nitrobenzyl-DOTA is obtained after anion-exchange column chromatography with elution of increasing concentration of ammonium acetate, for example.

Workup

  1. customThe tosyl protecting groups of 2-(p-nitrobenzyl)-N,N',N",N"'-tetrakis (tolylsulfonyl)-1,4,7,10-tetraazacyclododecane are removed
  2. customat 100° C.
  3. customfor 56 hours

Sources & evidence

ORD record
ord-3c0ec47ba50345a79e34eb70b5928560
Source dataset
uspto-grants-1996_07
Patent number
US05541287

Reaction notes

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