Hydrochloric Acid → 5,5'-(2,7-dihydroxyoctane-1,8-diyl)bis(acetylazanediyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide)

HRID 41831

Reaction equation

HRID 41831 reaction equation
[OH-:1].[K+].[C:3]([NH:6][C:7]1[C:8]([I:31])=[C:9]([C:23]([NH:25][CH2:26][CH:27]([OH:30])[CH2:28][OH:29])=[O:24])[C:10]([I:22])=[C:11]([C:20]=1[I:21])[C:12]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][OH:18])=[O:13])(=[O:5])[CH3:4].B(O)(O)O.[O:36]1[CH2:38][CH:37]1[CH2:39][CH2:40][CH2:41][CH2:42][CH:43]1[CH2:45][O:44]1.Cl>C(#N)C.O.O.CO>[OH:36][CH:37]([CH2:39][CH2:40][CH2:41][CH2:42][CH:43]([OH:44])[CH2:45][N:6]([C:7]1[C:20]([I:21])=[C:11]([C:12]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][OH:18])=[O:13])[C:10]([I:22])=[C:9]([C:8]=1[I:31])[C:23]([NH:25][CH2:26][CH:27]([OH:30])[CH2:28][OH:29])=[O:24])[C:3](=[O:1])[CH3:4])[CH2:38][N:6]([C:7]1[C:20]([I:21])=[C:11]([C:12]([NH:14][CH2:15][CH:16]([OH:19])[CH2:17][OH:18])=[O:13])[C:10]([I:22])=[C:9]([C:8]=1[I:31])[C:23]([NH:25][CH2:26][CH:27]([OH:30])[CH2:28][OH:29])=[O:24])[C:3](=[O:5])[CH3:4]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7628Boric AcidHCID 14797Potassium HydroxideHCID 170481,2:7,8-DiepoxyoctaneHCID 111153265-Acetamido-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide

Product 1

HCID 442189495,5'-(2,7-dihydroxyoctane-1,8-diyl)bis(acetylazanediyl)bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophthalamide)

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a stirred solution of water/methanol (4.9 ml, 2.5 ml) and potassium hydroxide (0.49 g, 8.7 mmol) at 40° C. was added 5-acetylamino-N,N′-bis-(2,3-dihydroxypropyl)-2,4,6-triiodo isophthalamide (5.0 g, 6.7 mmol). To the clear solution was then added boric acid (0.29 g, 4.6 mmol). The mixture was cooled to room temperature and pH adjusted to 12.6. 2-(4-oxiran-2-ylbutyl)oxirane (0.327 g, 2.3 mmol) was added. The pH of the solution was adjusted to the interval 12.6-13. The reaction was left over weekend. To the solution was added HCl (18%) to pH 4. Salts were removed by treatment with ion exchanger AMB200C and IRA67. The solution was filtered from the resin and evaporated. An aliquot of the crude material was purified by preparative HPLC (column Phenomenex Luna C18(2) 10 μm 250×50.0 mm, solvents: A=water and B=acetonitrile; gradient 07-13% B over 60 min; flow 50.0 ml/min, UV detection at 214 nm and 254 nm). The product was obtained in 639 mg after lyophilisation. Analysis by LC-MS (column Agilent Zorbax SB-Aq 3.5 μm 3.0×100 mm, solvents: A=water/0.1% formic acid and B=acetonitrile/0.1% formic acid; gradient 0-30% B over 20 min; flow 0.3 ml/min, UV detection at 214 and 254 nm, ESI-MS) gave two isomeric peaks eluting between 12.50-12.85 minutes with m/z 1636.6 (MH+) corresponding to the structure.

Workup

  1. waitThe reaction was left over weekend
  2. customSalts were removed by treatment with ion exchanger AMB200C and IRA67
  3. filtrationThe solution was filtered from the resin
  4. customevaporated
  5. customAn aliquot of the crude material was purified by preparative HPLC (column Phenomenex Luna C18(2) 10 μm 250×50.0 mm, solvents
  6. customThe product was obtained in 639 mg after lyophilisation
  7. waitgradient 0-30% B over 20 min
  8. customgave two isomeric peaks
  9. washeluting between 12.50-12.85 minutes with m/z 1636.6 (MH+) corresponding to the structure

Sources & evidence

ORD record
ord-6a184bdeff5f4c2d835dc5d3c5ea74fc
Source dataset
uspto-grants-2013_09
Patent number
US08535642B2

Linked notes

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